> top > docs > PMC:1564426 > annotations

PMC:1564426 JSONTXT

Annnotations TAB JSON ListView MergeView

craft-ca-core-ex-dev

Below, discontinuous spans are shown in the chain model. You can change it to the bag model.

Id Subject Object Predicate Lexical cue
T496 0-26 PR_EXT:000004122 denotes Adenomatous Polyposis Coli
T497 28-31 PR_EXT:000004122 denotes APC
T498 56-75 GO:0043588 denotes Development of Skin
T499 56-70 _FRAGMENT denotes Development of
T500 80-86 GO:0048538 denotes Thymus
T501 71-75 UBERON_EXT:zone_of_skin_or_skin_of_body denotes Skin
T502 80-86 UBERON:0002370 denotes Thymus
T503 157-161 SO_EXT:0000704 denotes gene
T504 162-165 PR_EXT:000004122 denotes Apc
T505 167-193 PR_EXT:000004122 denotes adenomatous polyposis coli
T506 214-235 GO:0016055 denotes Wnt signaling pathway
T507 309-313 NCBITaxon:10088 denotes mice
T508 318-321 PR_EXT:000004122 denotes Apc
T509 386-395 UBERON:0000922 denotes embryonic
T510 396-405 GO_EXT:fatality_or_lethality denotes lethality
T511 433-436 PR_EXT:000004122 denotes Apc
T512 467-473 SO:0000359 denotes floxed
T513 474-480 SO_EXT:0001023 denotes allele
T514 488-492 NCBITaxon:10088 denotes mice
T515 498-503 GO:0007618 denotes mated
T516 531-542 GO_EXT:recombinase denotes recombinase
T517 553-560 GO:0065007 denotes control
T518 568-573 NCBITaxon:9606 denotes human
T519 574-584 PR_EXT:000009454 denotes Keratin 14
T520 586-589 PR_EXT:000009454 denotes K14
T521 591-599 SO_EXT:0000167 denotes promoter
T522 620-644 CL:0002187 denotes basal cells of epidermis
T523 626-631 CL_GO_EXT:cell denotes cells
T524 626-634 _FRAGMENT denotes cells of
T525 655-675 CL:0000079 denotes stratified epithelia
T526 635-644 UBERON:0007376 denotes epidermis
T527 655-675 UBERON:0000486 denotes stratified epithelia
T528 677-681 NCBITaxon:10088 denotes Mice
T529 701-707 SO:0000359 denotes floxed
T530 708-714 SO_EXT:0001023 denotes allele
T531 735-738 PR_EXT:000009454 denotes K14
T532 743-752 SO_EXT:0000902 denotes transgene
T533 781-787 GO_EXT:biological_growth_entity_or_process denotes growth
T534 792-796 GO:0016265 denotes died
T535 872-875 PR_EXT:000009454 denotes K14
T536 889-892 PR_EXT:000004122 denotes Apc
T537 919-925 GO_EXT:biological_growth_entity_or_process denotes growth
T538 934-946 UBERON:0000924 denotes ectodermally
T539 955-973 UBERON:0006914 denotes squamous epithelia
T540 985-999 UBERON:0002073 denotes hair follicles
T541 1001-1006 UBERON:0001091 denotes teeth
T542 1012-1016 _FRAGMENT denotes oral
T543 1029-1038 UBERON:0002424 denotes epithelia
T544 1021-1038 UBERON:0001772 denotes corneal epithelia
T545 1097-1107 UBERON:0000483 denotes epithelial
T546 1116-1123 UBERON:0000479 denotes tissues
T547 1139-1145 UBERON:0002370 denotes thymus
T548 1160-1166 GO_EXT:biological_growth_entity_or_process denotes growth
T549 1170-1184 UBERON:0002073 denotes hair follicles
T550 1195-1205 UBERON:0004529 denotes appendages
T551 1221-1227 UBERON:0002370 denotes thymic
T552 1245-1248 PR_EXT:000009454 denotes K14
T553 1254-1257 PR_EXT:000004122 denotes Apc
T554 1265-1269 NCBITaxon:10088 denotes mice
T555 1282-1285 PR_EXT:000004122 denotes Apc
T556 1286-1290 SO_EXT:0000704 denotes gene
T557 1305-1314 UBERON:0000922 denotes embryonic
T558 1305-1320 CL:0002321 denotes embryonic cells
T559 1315-1320 CL_GO_EXT:cell denotes cells
T560 1332-1342 UBERON:0000483 denotes epithelial
T561 1332-1347 CL:0000066 denotes epithelial cell
T562 1343-1347 CL_GO_EXT:cell denotes cell
T563 1357-1363 UBERON:0000062 denotes organs
T564 1377-1387 UBERON:0000483 denotes epithelial
T565 1388-1399 UBERON:0003104 denotes mesenchymal
T2202 2771-2797 PR_EXT:000004122 denotes Adenomatous polyposis coli
T2203 2799-2802 PR_EXT:000004122 denotes APC
T2204 2823-2844 GO:0016055 denotes Wnt signaling pathway
T2205 2882-2890 GO:0065007 denotes regulate
T2206 2905-2914 PR_EXT:000002198 denotes β-catenin
T2207 2931-2940 PR_EXT:000002198 denotes β-catenin
T2208 2941-2951 GO:0065007 denotes regulation
T2209 2971-2976 NCBITaxon:9606 denotes human
T2210 2997-3000 PR_EXT:000004122 denotes APC
T2211 3041-3050 GO:0005829 denotes cytosolic
T2212 3051-3060 PR_EXT:000002198 denotes β-catenin
T2213 3092-3104 _FRAGMENT denotes migration to
T2214 3109-3116 GO:0051170 denotes nucleus
T2215 3109-3116 GO:0005634 denotes nucleus
T2216 3178-3181 PR_EXT:000004122 denotes APC
T2217 3223-3231 CL_GO_EXT:cell denotes cellular
T2218 3232-3240 CHEBI_PR_EXT:protein denotes proteins
T2219 3252-3258 PR_EXT:000004527 denotes axin-2
T2220 3260-3265 PR_EXT:000004527 denotes AXIN2
T2221 3268-3279 PR_EXT:000009235 denotes plakoglobin
T2222 3281-3284 PR_EXT:000009235 denotes JUP
T2223 3287-3291 PR_EXT:000004257 denotes Asef
T2224 3293-3300 PR_EXT:000004257 denotes ARHGEF4
T2225 3303-3343 PR_EXT:000009322 denotes kinesin superfamily–associated protein 3
T2226 3334-3341 CHEBI_PR_EXT:protein denotes protein
T2227 3345-3351 PR_EXT:000009322 denotes KIFAP3
T2228 3354-3357 PR_EXT:000010170 denotes EB1
T2229 3359-3365 PR_EXT:000010170 denotes MAPRE1
T2230 3368-3380 GO:0005874 denotes microtubules
T2231 3390-3395 NCBITaxon:9606 denotes human
T2232 3396-3403 SO_EXT:0000853 denotes homolog
T2233 3396-3429 PR_EXT:000006511 denotes homolog of Drosophila discs large
T2234 3407-3417 NCBITaxon:7215 denotes Drosophila
T2235 3431-3435 PR_EXT:000006511 denotes DLG1
T2236 3470-3473 PR_EXT:000004122 denotes APC
T2237 3490-3498 GO:0065007 denotes regulate
T2238 3504-3512 CL_GO_EXT:cell denotes cellular
T2239 3539-3547 CL_GO_EXT:cell denotes cellular
T2240 3548-3556 GO_PATO_EXT:biological_adhesion_entity_or_process denotes adhesion
T2241 3558-3570 GO:0005856 denotes cytoskeletal
T2242 3585-3595 GO:0065007 denotes regulation
T2243 3599-3610 PR_EXT:000009235 denotes plakoglobin
T2244 3619-3632 _FRAGMENT denotes regulation of
T2245 3637-3647 GO:0051726 denotes cell cycle
T2246 3652-3661 GO:0042981 denotes apoptosis
T2247 3637-3641 CL_GO_EXT:cell denotes cell
T2248 3678-3707 GO:0098722 denotes asymmetric stem cell division
T2249 3689-3698 CL:0000034 denotes stem cell
T2250 3694-3698 CL_GO_EXT:cell denotes cell
T2251 3713-3741 GO:2000114 denotes control of cell polarization
T2252 3724-3728 CL_GO_EXT:cell denotes cell
T2253 3749-3752 PR_EXT:000004122 denotes APC
T2254 3775-3779 SO_EXT:0000704 denotes gene
T2255 3789-3798 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2256 3802-3805 PR_EXT:000004122 denotes APC
T2257 3858-3863 UBERON:0001155 denotes colon
T2258 3868-3874 UBERON:0001052 denotes rectum
T2259 3876-3885 GO:0030849 denotes Autosomal
T2260 3904-3913 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2261 3917-3920 PR_EXT:000004122 denotes APC
T2262 4056-4066 UBERON:0012652 denotes colorectal
T2263 4116-4126 UBERON:0012652 denotes colorectal
T2264 4169-4173 UBERON:0000104 denotes life
T2265 4196-4206 UBERON:0012652 denotes colorectal
T2266 4223-4234 NCBITaxon:1 denotes individuals
T2267 4252-4259 UBERON:0001155 denotes colonic
T2268 4292-4314 UBERON:0001555 denotes gastrointestinal tract
T2269 4353-4379 UBERON:0001782 denotes retinal pigment epithelium
T2270 4361-4368 CHEBI_EXT:26130 denotes pigment
T2271 4414-4423 UBERON:0002397 denotes maxillary
T2272 4428-4436 UBERON:0004288 denotes skeletal
T2273 4437-4442 UBERON:0001474 denotes bones
T2274 4448-4454 UBERON:0001091 denotes dental
T2275 4503-4506 PR_EXT:000004122 denotes APC
T2276 4507-4511 SO_EXT:0000704 denotes gene
T2277 4531-4544 UBERON:0000467 denotes organ systems
T2278 4567-4570 PR_EXT:000004122 denotes APC
T2279 4592-4597 NCBITaxon:9606 denotes human
T2280 4598-4608 UBERON:0012652 denotes colorectal
T2281 4655-4661 UBERON:0000479 denotes tissue
T2282 4739-4766 GO:0030111 denotes regulation of Wnt signaling
T2283 4770-4779 UBERON:0000922 denotes embryonic
T2284 4770-4797 GO:0009880 denotes embryonic pattern formation
T2285 4802-4818 _FRAGMENT denotes morphogenesis of
T2286 4824-4830 GO:0009887 denotes organs
T2287 4824-4830 UBERON:0000062 denotes organs
T2288 4861-4864 PR_EXT:000004122 denotes APC
T2289 4892-4899 UBERON:0001155 denotes colonic
T2290 4900-4907 UBERON:0000479 denotes tissues
T2291 4970-4976 NCBITaxon:9606 denotes humans
T2292 5017-5020 PR_EXT:000004122 denotes Apc
T2293 5050-5054 NCBITaxon:10088 denotes mice
T2294 5076-5079 PR_EXT:000004122 denotes Apc
T2295 5080-5088 SO_EXT:sequence_alteration_entity_or_process denotes mutation
T2296 5098-5109 SO_EXT:0000704 denotes genetically
T2297 5110-5118 SO_EXT:sequence_alteration_process denotes modified
T2298 5119-5124 NCBITaxon:10088 denotes mouse
T2299 5137-5140 PR_EXT:000004122 denotes Apc
T2300 5225-5241 UBERON:0005409 denotes gastrointestinal
T2301 5291-5296 NCBITaxon:10088 denotes Mouse
T2302 5297-5304 UBERON:0000922 denotes embryos
T2303 5333-5340 SO_EXT:0000704 denotes genetic
T2304 5341-5353 SO_EXT:sequence_alteration_entity_or_process denotes modification
T2306 5365-5378 GO:0009790 denotes embryogenesis
T2307 5425-5437 GO:0007369 denotes gastrulation
T2308 5494-5497 PR_EXT:000004122 denotes Apc
T2309 5532-5539 UBERON:0000479 denotes tissues
T2310 5557-5562 NCBITaxon:10088 denotes mouse
T2311 5599-5607 SO_EXT:sequence_alteration_process denotes modified
T2312 5608-5614 SO_EXT:0001023 denotes allele
T2313 5619-5623 GO:0007618 denotes mate
T2314 5634-5639 NCBITaxon:10088 denotes mouse
T2315 5668-5680 SO_EXT:sequence_alteration_entity_or_process denotes modification
T2316 5700-5706 SO_EXT:0001023 denotes allele
T2317 5719-5723 CL_GO_EXT:cell denotes cell
T2318 5756-5759 PR_EXT:000004122 denotes Apc
T2319 5773-5787 UBERON:0000105 denotes stages of life
T2320 5817-5821 NCBITaxon:10088 denotes mice
T2321 5862-5868 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2322 5869-5875 SO_EXT:0001023 denotes allele
T2323 5879-5882 PR_EXT:000004122 denotes Apc
T2324 5884-5887 PR_EXT:000004122 denotes Apc
T2325 5899-5903 NCBITaxon:10088 denotes mice
T2326 5909-5914 GO:0007618 denotes mated
T2327 5942-5953 GO_EXT:recombinase denotes recombinase
T2328 5964-5971 GO:0065007 denotes control
T2329 5979-5984 NCBITaxon:9606 denotes human
T2330 5985-5995 PR_EXT:000009454 denotes Keratin 14
T2331 5997-6000 PR_EXT:000009454 denotes K14
T2332 6002-6010 SO_EXT:0000167 denotes promoter
T2333 6031-6055 CL:0002187 denotes basal cells of epidermis
T2334 6037-6042 CL_GO_EXT:cell denotes cells
T2335 6037-6045 _FRAGMENT denotes cells of
T2336 6066-6086 CL:0000079 denotes stratified epithelia
T2337 6046-6055 UBERON:0007376 denotes epidermis
T2338 6066-6086 UBERON:0000486 denotes stratified epithelia
T2339 6108-6111 PR_EXT:000009454 denotes K14
T2340 6112-6120 SO_EXT:0000167 denotes promoter
T2341 6136-6139 PR_EXT:000004122 denotes Apc
T2342 6161-6175 _FRAGMENT denotes development of
T2343 6184-6190 GO:0048513 denotes organs
T2344 6184-6190 UBERON:0000062 denotes organs
T2345 6214-6224 UBERON:0000483 denotes epithelial
T2346 6225-6236 UBERON:0003104 denotes mesenchymal
T2347 6261-6274 UBERON:0002073 denotes hair follicle
T2348 6276-6281 UBERON:0001091 denotes teeth
T2349 6287-6293 UBERON:0002370 denotes thymus
T2350 6311-6319 PATO_UBERON_EXT:neonate_or_newborn denotes neonatal
T2351 6320-6325 GO:0016265 denotes death
T2352 6329-6333 NCBITaxon:10088 denotes mice
T2353 6349-6352 PR_EXT:000004122 denotes Apc
T2354 6377-6405 GO:0001709 denotes determinations of cell fates
T2355 6395-6399 CL_GO_EXT:cell denotes cell
T2356 6417-6426 UBERON:0000922 denotes embryonic
T2357 6417-6438 GO:0009790 denotes embryonic development
T2358 6466-6472 UBERON:0000479 denotes tissue
T2359 6482-6492 GO:0065007 denotes regulation
T2360 6496-6505 PR_EXT:000002198 denotes β-catenin
T2361 6520-6524 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T2362 6530-6540 UBERON:0004529 denotes appendages
T2363 6553-6559 UBERON:0002370 denotes thymus
T4427 6608-6612 NCBITaxon:10088 denotes Mice
T4428 6640-6643 PR_EXT:000004122 denotes Apc
T4429 6647-6666 GO:0043588 denotes development of skin
T4430 6662-6666 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T4431 6675-6685 UBERON:0004529 denotes appendages
T4432 6703-6707 SO_EXT:0000346 denotes loxP
T4433 6746-6754 SO_EXT:sequence_alteration_entity_or_process denotes mutation
T4434 6762-6765 PR_EXT:000004122 denotes Apc
T4435 6766-6770 SO_EXT:0000704 denotes gene
T4436 6774-6778 NCBITaxon:10088 denotes mice
T4437 6795-6804 UBERON:0000922 denotes embryonic
T4438 6795-6809 _FRAGMENT denotes embryonic stem
T4439 6815-6820 CL:0002322 denotes cells
T4440 6811-6813 _FRAGMENT denotes ES
T4441 6815-6820 CL_GO_EXT:cell denotes cells
T4442 6825-6829 NCBITaxon:10088 denotes mice
T4443 6842-6845 PR_EXT:000004122 denotes Apc
T4444 6846-6852 SO_EXT:0001023 denotes allele
T4445 6878-6888 SO_EXT:0000346 denotes loxP sites
T4446 6889-6897 SO:0000357 denotes flanking
T4447 6898-6901 PR_EXT:000004122 denotes Apc
T4448 6902-6906 SO_EXT:0000147 denotes exon
T4449 6924-6927 PR_EXT:P03870 denotes FLP
T4450 6924-6946 _FRAGMENT denotes FLP recognition target
T4451 6953-6958 SO_EXT:0000350 denotes sites
T4452 6948-6951 _FRAGMENT denotes FRT
T4453 6959-6967 SO:0000357 denotes flanking
T4454 6968-6971 GO_EXT:phosphoglycerate_kinase denotes PGK
T4455 6972-6980 CHEBI:7507 denotes neomycin
T4456 6991-6999 SO_EXT:0005853 denotes cassette
T4457 7038-7041 PR_EXT:000004122 denotes Apc
T4458 7046-7052 SO_EXT:0001023 denotes allele
T4459 7054-7055 CHEBI_GO_EXT:neomycin_or_neomycin_phosphotransferase denotes N
T4460 7060-7068 CHEBI:7507 denotes neomycin
T4461 7069-7077 SO_EXT:0005853 denotes cassette
T4462 7082-7085 GO_EXT:phosphoglycerate_kinase denotes PGK
T4463 7086-7094 CHEBI:7507 denotes neomycin
T4464 7095-7103 SO_EXT:0005853 denotes cassette
T4465 7108-7116 SO_EXT:sequence_insertion_process denotes inserted
T4466 7129-7144 GO_EXT:transcription denotes transcriptional
T4467 7160-7163 PR_EXT:000004122 denotes Apc
T4468 7167-7173 SO_EXT:0000188 denotes intron
T4469 7195-7199 SO_EXT:0000704 denotes gene
T4470 7205-7209 _FRAGMENT denotes loxP
T4471 7218-7223 SO_EXT:0000346 denotes sites
T4472 7214-7223 SO_EXT:0000350 denotes FRT sites
T4473 7256-7269 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T4474 7283-7288 NCBITaxon:10088 denotes mouse
T4475 7315-7327 SO_EXT:sequence_alteration_entity_or_process denotes modification
T4476 7364-7366 CL:0002322 denotes ES
T4477 7367-7373 SO_EXT:sequence_cloned_entity denotes clones
T4478 7405-7411 GO_PATO_EXT:biological_behavior denotes behave
T4479 7435-7438 PR_EXT:000004122 denotes Apc
T4480 7443-7444 SO_EXT:normal_or_wild_type_or_present denotes +
T4481 7445-7449 NCBITaxon:10088 denotes mice
T4482 7493-7496 PR_EXT:000004122 denotes Apc
T4483 7500-7501 SO_EXT:normal_or_wild_type_or_present denotes +
T4484 7502-7506 NCBITaxon:10088 denotes mice
T4485 7544-7547 PR_EXT:000004122 denotes Apc
T4486 7561-7564 PR_EXT:000004122 denotes Apc
T4487 7569-7575 SO_EXT:0001023 denotes allele
T4488 7593-7596 GO_EXT:phosphoglycerate_kinase denotes PGK
T4489 7597-7605 CHEBI:7507 denotes neomycin
T4490 7606-7614 SO_EXT:0005853 denotes cassette
T4491 7637-7647 SO_EXT:0000346 denotes loxP sites
T4492 7655-7662 SO_EXT:0000188 denotes introns
T4493 7663-7671 SO:0000357 denotes flanking
T4494 7672-7676 SO_EXT:0000147 denotes exon
T4495 7705-7713 SO_EXT:sequence_deletion_process denotes deleting
T4496 7714-7718 SO_EXT:0000147 denotes exon
T4497 7725-7729 NCBITaxon:10088 denotes mice
T4498 7745-7748 PR_EXT:000004122 denotes Apc
T4499 7752-7753 SO_EXT:normal_or_wild_type_or_present denotes +
T4500 7754-7758 NCBITaxon:10088 denotes mice
T4501 7835-7838 PR_EXT:000004122 denotes Apc
T4502 7851-7854 PR_EXT:000004122 denotes Apc
T4503 7859-7860 SO_EXT:normal_or_wild_type_or_present denotes +
T4504 7866-7872 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T4505 7873-7879 SO_EXT:0001023 denotes allele
T4506 7881-7884 PR_EXT:000004122 denotes Apc
T4507 7896-7900 SO_EXT:0000147 denotes exon
T4508 7921-7931 SO_EXT:0000673 denotes transcript
T4509 7945-7949 SO_EXT:0000147 denotes exon
T4510 7966-7974 _FRAGMENT denotes shift in
T4511 7986-7999 GO_SO_EXT:frameshift_entity_or_process denotes reading frame
T4512 8016-8049 SO_EXT:0001587 denotes premature chain termination codon
T4513 8088-8097 SO_EXT:sequence_truncation_process denotes truncated
T4514 8098-8109 CHEBI_SO_EXT:polypeptide denotes polypeptide
T4515 8122-8124 CHEBI_SO_EXT:amino_acid denotes aa
T4516 8159-8161 CHEBI_SO_EXT:amino_acid denotes aa
T4517 8187-8190 PR_EXT:000004122 denotes Apc
T4518 8191-8198 CHEBI_PR_EXT:protein denotes protein
T4519 9791-9795 UBERON:0002415 denotes tail
T4520 9796-9799 CHEBI_SO_EXT:DNA denotes DNA
T4521 9826-9829 PR_EXT:000004122 denotes Apc
T4522 9838-9841 PR_EXT:000004122 denotes Apc
T4523 9891-9899 SO_EXT:sequence_alteration_process denotes modified
T4524 9900-9903 PR_EXT:000004122 denotes Apc
T4525 9904-9910 SO_EXT:0001023 denotes allele
T4526 9924-9928 NCBITaxon:10088 denotes Mice
T4527 9955-9958 PR_EXT:000004122 denotes Apc
T4528 9963-9971 SO_EXT:sequence_alteration_entity_or_process denotes mutation
T4529 10016-10024 UBERON:0000104 denotes lifespan
T4530 10067-10075 SO_EXT:sequence_deletion_entity_or_process denotes deletion
T4531 10079-10083 SO_EXT:0000147 denotes exon
T4532 10145-10148 PR_EXT:000004122 denotes Apc
T4533 10149-10161 SO_EXT:gene_product denotes gene product
T4534 10163-10166 PR_EXT:000004122 denotes Apc
T4535 10171-10172 SO_EXT:normal_or_wild_type_or_present denotes +
T4536 10173-10177 NCBITaxon:10088 denotes mice
T4537 10253-10259 UBERON:0001052 denotes rectal
T4538 10345-10348 PR_EXT:000004122 denotes Apc
T4539 10353-10354 SO_EXT:normal_or_wild_type_or_present denotes +
T4540 10367-10372 NCBITaxon:10088 denotes mouse
T4541 10386-10389 PR_EXT:000004122 denotes Apc
T4542 10394-10395 SO_EXT:normal_or_wild_type_or_present denotes +
T4543 10396-10400 NCBITaxon:10088 denotes mice
T4544 10438-10448 UBERON:0000160 denotes intestinal
T4545 10477-10482 GO:0016265 denotes death
T4546 10512-10521 SO_EXT:wild_type_entity_or_quality denotes wild-type
T4547 10522-10525 PR_EXT:000004122 denotes Apc
T4548 10593-10603 UBERON:0000160 denotes intestinal
T4549 10616-10619 PR_EXT:000004122 denotes Apc
T4550 10624-10625 SO_EXT:normal_or_wild_type_or_present denotes +
T4551 10626-10630 NCBITaxon:10088 denotes mice
T4552 10643-10656 GO_EXT:transcription denotes transcription
T4553 10661-10672 GO:0006412 denotes translation
T4554 10704-10713 SO_EXT:sequence_truncation_process denotes truncated
T4555 10714-10717 PR_EXT:000004122 denotes Apc
T4556 10792-10801 SO_EXT:wild_type_entity_or_quality denotes wild-type
T4557 10802-10805 PR_EXT:000004122 denotes Apc
T4558 10825-10832 SO_EXT:0001023 denotes allelic
T4559 10843-10849 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T4560 10850-10856 SO_EXT:0001023 denotes allele
T4561 10902-10906 PATO_UBERON_EXT:male_or_bearer_of_maleness denotes male
T4562 10907-10911 NCBITaxon:10088 denotes mice
T4563 10916-10919 PR_EXT:000004122 denotes Apc
T4564 10924-10925 SO_EXT:normal_or_wild_type_or_present denotes +
T4565 10926-10933 PATO_UBERON_EXT:female_or_bearer_of_femaleness denotes females
T4566 10985-10990 GO:0001967 denotes nurse
T4567 11001-11005 NCBITaxon_UBERON_EXT:pup denotes pups
T4568 11037-11040 PR_EXT:000004122 denotes Apc
T4569 11044-11045 SO_EXT:normal_or_wild_type_or_present denotes +
T4570 11046-11050 NCBITaxon:10088 denotes mice
T4571 11081-11084 PR_EXT:000004122 denotes Apc
T4572 11181-11184 PR_EXT:000004122 denotes Apc
T4573 11188-11194 SO_EXT:0001023 denotes allele
T4574 11202-11206 NCBITaxon:10088 denotes mice
T4575 11231-11235 NCBITaxon:10088 denotes mice
T4576 11240-11243 PR_EXT:000004122 denotes Apc
T4577 11247-11253 SO_EXT:0001023 denotes allele
T4578 11314-11323 SO_EXT:wild_type_entity_or_quality denotes wild-type
T4579 11371-11374 PR_EXT:000004122 denotes Apc
T4580 11378-11384 SO_EXT:0001023 denotes allele
T4581 11404-11413 SO_EXT:wild_type_entity_or_quality denotes wild-type
T4582 11414-11420 SO_EXT:0001023 denotes allele
T4583 11437-11440 PR_EXT:000004122 denotes Apc
T4584 11448-11454 PATO_UBERON_EXT:female_or_bearer_of_femaleness denotes female
T4585 11460-11463 PR_EXT:000004122 denotes Apc
T4586 11468-11469 SO_EXT:normal_or_wild_type_or_present denotes +
T4587 11470-11474 PATO_UBERON_EXT:male_or_bearer_of_maleness denotes male
T4588 11475-11480 NCBITaxon:10088 denotes mouse
T4589 11496-11499 PR_EXT:000004122 denotes Apc
T4590 11534-11538 GO:0007567 denotes born
T4591 11595-11605 SO_EXT:0000346 denotes loxP sites
T4592 11609-11616 SO_EXT:0000188 denotes introns
T4593 11617-11625 SO:0000357 denotes flanking
T4594 11626-11630 SO_EXT:0000147 denotes exon
T4595 11680-11683 PR_EXT:000004122 denotes Apc
T4596 11684-11688 SO_EXT:0000704 denotes gene
T7493 11691-11694 PR_EXT:000009454 denotes K14
T7494 11710-11713 PR_EXT:000004122 denotes Apc
T7495 11732-11738 GO_EXT:biological_growth_entity_or_process denotes Growth
T7496 11761-11770 GO_EXT:fatality_or_lethality denotes Lethality
T7497 11788-11796 SO_EXT:sequence_alteration_entity_or_process denotes mutation
T7498 11800-11803 PR_EXT:000004122 denotes Apc
T7499 11809-11814 CL_GO_EXT:cell denotes cells
T7500 11815-11825 GO:0010467 denotes expressing
T7501 11826-11829 PR_EXT:000009454 denotes K14
T7502 11846-11853 CL:0002322 denotes ES cell
T7503 11849-11853 CL_GO_EXT:cell denotes cell
T7504 11867-11870 PR_EXT:000004122 denotes Apc
T7505 11874-11875 SO_EXT:normal_or_wild_type_or_present denotes +
T7506 11876-11880 NCBITaxon:10088 denotes mice
T7507 11886-11889 PR_EXT:000009454 denotes K14
T7508 11894-11905 GO_EXT:recombinase denotes recombinase
T7509 11906-11910 NCBITaxon:10088 denotes mice
T7510 11939-11942 PR_EXT:000009454 denotes K14
T7511 11948-11951 PR_EXT:000004122 denotes Apc
T7512 11955-11956 SO_EXT:normal_or_wild_type_or_present denotes +
T7513 11957-11961 NCBITaxon:10088 denotes mice
T7514 12006-12009 PR_EXT:000009454 denotes K14
T7515 12015-12018 PR_EXT:000004122 denotes Apc
T7516 12022-12023 SO_EXT:normal_or_wild_type_or_present denotes +
T7517 12024-12029 PATO_UBERON_EXT:male_or_bearer_of_maleness denotes males
T7518 12046-12049 PR_EXT:000004122 denotes Apc
T7519 12057-12064 PATO_UBERON_EXT:female_or_bearer_of_femaleness denotes females
T7520 12106-12113 CL:0000023 denotes oocytes
T7521 12117-12120 PR_EXT:000009454 denotes K14
T7522 12134-12141 PATO_UBERON_EXT:female_or_bearer_of_femaleness denotes females
T7523 12152-12156 NCBITaxon:10088 denotes mice
T7524 12214-12218 NCBITaxon:10088 denotes mice
T7525 12352-12355 PR_EXT:000009454 denotes K14
T7526 12356-12364 SO_EXT:0000167 denotes promoter
T7527 12384-12393 UBERON:0007376 denotes epidermal
T7528 12384-12398 CL:0000362 denotes epidermal cell
T7529 12394-12398 CL_GO_EXT:cell denotes cell
T7530 12399-12407 SO_EXT:0000167 denotes promoter
T7531 12423-12433 GO:0010467 denotes expression
T7532 12441-12452 GO:0007067 denotes mitotically
T7533 12460-12465 CL_GO_EXT:cell denotes cells
T7534 12460-12468 _FRAGMENT denotes cells of
T7535 12473-12482 CL:0000362 denotes epidermis
T7536 12473-12482 UBERON:0007376 denotes epidermis
T7537 12491-12501 UBERON:0004529 denotes appendages
T7538 12512-12516 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T7539 12556-12574 UBERON:0000924 denotes embryonic ectoderm
T7540 12606-12616 UBERON:0000924 denotes ectodermal
T7541 12626-12635 UBERON:0000922 denotes embryonic
T7542 12667-12677 GO:0010467 denotes expression
T7543 12681-12684 PR_EXT:000009454 denotes K14
T7544 12702-12719 UBERON:0003846 denotes thymic epithelial
T7545 12702-12725 CL:0002293 denotes thymic epithelial cells
T7546 12720-12725 CL_GO_EXT:cell denotes cells
T7547 12727-12731 CL:0002293 denotes TECs
T7548 12740-12750 _FRAGMENT denotes medulla of
T7549 12758-12764 UBERON:0002124 denotes thymus
T7550 12799-12803 NCBITaxon_UBERON_EXT:pup denotes pups
T7551 12864-12867 PR_EXT:000009454 denotes K14
T7552 12873-12876 PR_EXT:000004122 denotes Apc
T7553 12880-12881 SO_EXT:normal_or_wild_type_or_present denotes +
T7554 12886-12889 PR_EXT:000004122 denotes Apc
T7555 12897-12901 NCBITaxon:10088 denotes mice
T7556 12907-12913 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7557 12914-12918 NCBITaxon:10088 denotes mice
T7558 12926-12934 SO_EXT:genotype_or_entity_with_genotype denotes genotype
T7559 12935-12938 PR_EXT:000009454 denotes K14
T7560 12944-12947 PR_EXT:000004122 denotes Apc
T7561 12970-12976 SO_EXT:sequence_altered_entity denotes mutant
T7562 12983-12987 GO:0007567 denotes born
T7563 13022-13029 SO_EXT:sequence_altered_entity denotes mutants
T7564 13148-13156 PATO_UBERON_EXT:neonate_or_newborn denotes neonatal
T7565 13157-13166 GO_EXT:fatality_or_lethality denotes lethality
T7566 13173-13180 SO_EXT:sequence_altered_entity denotes mutants
T7567 13214-13219 GO:0007567 denotes birth
T7568 13248-13252 UBERON_EXT:body denotes body
T7569 13268-13271 NCBITaxon_UBERON_EXT:pup denotes pup
T7570 13297-13301 NCBITaxon_UBERON_EXT:pup denotes pups
T7571 13307-13311 GO:0007567 denotes born
T7572 13370-13373 PR_EXT:000009454 denotes K14
T7573 13379-13382 PR_EXT:000004122 denotes Apc
T7574 13424-13431 SO_EXT:sequence_altered_entity denotes mutants
T7575 13437-13441 GO:0007567 denotes born
T7576 13482-13488 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7577 13489-13493 NCBITaxon_UBERON_EXT:pup denotes pups
T7578 13499-13505 GO:0001967 denotes nursed
T7579 13530-13534 UBERON:0001913 denotes milk
T7580 13544-13552 UBERON:0000945 denotes stomachs
T7581 13585-13590 GO:0007567 denotes birth
T7582 13637-13642 GO:0007567 denotes natal
T7583 13692-13698 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7584 13699-13703 NCBITaxon_UBERON_EXT:pup denotes pups
T7585 13782-13786 GO:0016265 denotes died
T7586 13823-13830 SO_EXT:sequence_altered_entity denotes mutants
T7587 15267-15274 UBERON:0000922 denotes embryos
T7588 15291-15294 CHEBI_EXT:37958 denotes dye
T7589 15319-15328 UBERON:0007376 denotes epidermal
T7590 15428-15435 SO_EXT:sequence_altered_entity denotes mutants
T7591 15479-15482 CHEBI_EXT:37958 denotes dye
T7592 15504-15513 UBERON:0007376 denotes epidermal
T7593 15555-15564 UBERON:0000922 denotes embryonic
T7594 15617-15624 SO_EXT:sequence_altered_entity denotes mutants
T7595 15656-15663 SO_EXT:sequence_altered_entity denotes mutants
T7596 15702-15714 GO_PATO_EXT:biological_pigmentation_process_or_quality denotes pigmentation
T7597 15724-15733 UBERON:0008200 denotes foreheads
T7598 15780-15784 UBERON:0000033 denotes head
T7599 15788-15792 UBERON:0002415 denotes tail
T7600 15800-15813 UBERON:0001691 denotes external ears
T7601 15817-15823 UBERON:0001757 denotes pinnae
T7602 15857-15866 CHEBI_EXT:26130 denotes pigmented
T7603 15932-15939 SO_EXT:sequence_altered_entity denotes mutants
T7604 15983-15988 GO:0007567 denotes birth
T7605 16023-16027 GO:0040007 denotes grew
T7606 16044-16050 GO_EXT:biological_growth_entity_or_process denotes Growth
T7607 16054-16065 UBERON:0010509 denotes pelage hair
T7608 16095-16102 SO_EXT:sequence_altered_entity denotes mutants
T7609 16125-16132 SO_EXT:sequence_altered_entity denotes mutants
T7610 16138-16142 UBERON:0001037 denotes hair
T7611 16164-16168 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T7612 16233-16245 UBERON:0010166 denotes coat of hair
T7613 16276-16290 UBERON:0003451 denotes lower incisors
T7614 16360-16367 SO_EXT:sequence_altered_entity denotes mutants
T7615 16388-16395 NCBITaxon:33208 denotes Animals
T7616 16482-16491 UBERON:0006378 denotes vibrissae
T7617 16510-16522 UBERON:0010509 denotes pelage hairs
T7618 16580-16584 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T7619 16610-16614 UBERON:0001690 denotes ears
T7620 16616-16623 UBERON:0001711 denotes eyelids
T7621 16625-16633 UBERON:0008200 denotes forehead
T7622 16635-16639 UBERON:0000004 denotes nose
T7623 16645-16649 UBERON_EXT:paw denotes paws
T7624 16720-16727 NCBITaxon:33208 denotes animals
T7625 16746-16750 UBERON:0000970 denotes eyes
T7626 16829-16833 UBERON_EXT:body denotes body
T7627 16864-16871 SO_EXT:sequence_altered_entity denotes mutants
T7628 17037-17044 SO_EXT:sequence_altered_entity denotes mutants
T7629 17050-17055 UBERON:0001091 denotes tooth
T7630 17069-17077 UBERON:0001098 denotes incisors
T7631 17081-17087 UBERON:0003655 denotes molars
T7632 17099-17107 UBERON:0000945 denotes stomachs
T7633 17149-17153 CHEBI_EXT:33290 denotes food
T7634 17268-17274 GO:0007631 denotes ingest
T7635 17281-17285 CHEBI_EXT:33290 denotes food
T7636 17325-17329 UBERON_EXT:body denotes body
T7637 17352-17356 UBERON:0001037 denotes hair
T7638 17357-17363 GO_EXT:biological_growth_entity_or_process denotes growth
T7639 17390-17396 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7640 17397-17401 NCBITaxon_UBERON_EXT:pup denotes pups
T7641 17580-17585 GO:0016265 denotes death
T7642 17589-17596 SO_EXT:sequence_altered_entity denotes mutants
T7643 17603-17609 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7644 17610-17614 NCBITaxon_UBERON_EXT:pup denotes pups
T7645 17620-17624 GO:0007567 denotes born
T7646 17635-17639 GO:0016265 denotes died
T7647 17725-17731 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7648 17816-17819 PR_EXT:000004122 denotes Apc
T7649 17820-17828 SO_EXT:sequence_deletion_entity_or_process denotes deletion
T7650 17854-17861 SO_EXT:0000704 denotes genetic
T7651 17943-17949 UBERON:0000062 denotes organs
T7652 17971-17978 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutants
T7653 17980-17985 UBERON:0002370 denotes thymi
T7654 18190-18196 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7655 18197-18202 UBERON:0002370 denotes thymi
T7656 18214-18220 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7657 18221-18225 NCBITaxon:10088 denotes mice
T7658 18267-18273 UBERON:0000479 denotes tissue
T7659 18294-18300 SO_EXT:sequence_altered_entity_or_alteration_process denotes Mutant
T7660 18301-18305 NCBITaxon:10088 denotes mice
T7661 18333-18341 UBERON:0004288 denotes skeletal
T7662 18369-18377 UBERON:0004288 denotes skeletal
T7663 18399-18403 NCBITaxon:10088 denotes mice
T7664 18417-18429 CHEBI:16866 denotes Alizarin red
T7665 18472-18478 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7666 18479-18483 NCBITaxon:10088 denotes mice
T7667 18491-18506 UBERON:0001684 denotes mandibular bone
T7668 18532-18538 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T7669 18539-18543 NCBITaxon:10088 denotes mice
T7670 18580-18598 UBERON:0003450 denotes maxillary incisors
T7671 18580-18589 _FRAGMENT denotes maxillary
T7672 18603-18609 UBERON:0003666 denotes molars
T7673 18650-18658 UBERON:0004288 denotes skeletal
T9516 18675-18683 SO_EXT:genotype_or_entity_with_genotype denotes Genotype
T9517 18689-18695 UBERON:0000479 denotes Tissue
T9518 18705-18715 GO:0010467 denotes Expression
T9519 18723-18732 SO_EXT:sequence_truncation_process denotes Truncated
T9520 18733-18736 PR_EXT:000004122 denotes Apc
T9521 18737-18748 SO_EXT:0000673 denotes Transcripts
T9522 18763-18772 CHEBI_EXT:polyatomic_entity_or_group denotes molecular
T9523 18788-18791 PR_EXT:000009454 denotes K14
T9524 18805-18818 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T9525 18852-18859 SO_EXT:sequence_deletion_process denotes deleted
T9526 18860-18863 PR_EXT:000004122 denotes Apc
T9527 18865-18868 PR_EXT:000004122 denotes Apc
T9528 18874-18881 SO_EXT:0001023 denotes alleles
T9529 18883-18894 SO_EXT:genomic_DNA denotes Genomic DNA
T9530 18891-18894 CHEBI_SO_EXT:DNA denotes DNA
T9531 18914-18919 UBERON:0002107 denotes liver
T9532 18921-18927 UBERON:0002370 denotes thymus
T9533 18933-18937 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T9534 18958-18967 SO_EXT:genotype_or_entity_with_genotype denotes genotypes
T9535 18969-18972 PR_EXT:000009454 denotes K14
T9536 18978-18981 PR_EXT:000004122 denotes Apc
T9537 18990-18993 PR_EXT:000009454 denotes K14
T9538 18999-19002 PR_EXT:000004122 denotes Apc
T9539 19006-19007 SO_EXT:normal_or_wild_type_or_present denotes +
T9540 19009-19012 PR_EXT:000004122 denotes Apc
T9541 19025-19028 PR_EXT:000004122 denotes Apc
T9542 19032-19033 SO_EXT:normal_or_wild_type_or_present denotes +
T9543 19049-19060 SO_EXT:genomic_DNA denotes genomic DNA
T9544 19057-19060 CHEBI_SO_EXT:DNA denotes DNA
T9545 19072-19079 UBERON:0000479 denotes tissues
T9546 19096-19099 PR_EXT:000004122 denotes Apc
T9547 19104-19110 SO_EXT:0001023 denotes allele
T9548 19116-19118 SO_EXT:0000028 denotes bp
T9549 19155-19159 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T9550 19164-19170 UBERON:0002370 denotes thymus
T9551 19178-19181 PR_EXT:000009454 denotes K14
T9552 19195-19199 NCBITaxon:10088 denotes mice
T9553 19217-19223 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T9554 19224-19227 PR_EXT:000004122 denotes Apc
T9555 19228-19234 SO_EXT:0001023 denotes allele
T9556 19242-19248 UBERON:0002370 denotes thymus
T9557 19252-19255 PR_EXT:000009454 denotes K14
T9558 19261-19264 PR_EXT:000004122 denotes Apc
T9559 19268-19269 SO_EXT:normal_or_wild_type_or_present denotes +
T9560 19270-19274 NCBITaxon:10088 denotes mice
T9561 19311-19314 CHEBI_SO_EXT:DNA denotes DNA
T9562 19324-19328 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T9563 19341-19347 NCBITaxon:33208 denotes animal
T9564 19357-19364 UBERON:0000479 denotes tissues
T9565 19377-19384 SO_EXT:sequence_altered_entity denotes mutants
T9566 19450-19455 UBERON:0002107 denotes liver
T9567 19459-19462 PR_EXT:000009454 denotes K14
T9568 19493-19496 PR_EXT:000009454 denotes K14
T9569 19510-19515 NCBITaxon:10088 denotes mouse
T9570 19516-19523 UBERON:0000479 denotes tissues
T9571 19564-19577 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T9572 19601-19607 UBERON:0000479 denotes tissue
T9573 19631-19635 NCBITaxon:10088 denotes mice
T9574 19651-19654 PR_EXT:000009454 denotes K14
T9575 20243-20246 PR_EXT:000004122 denotes Apc
T9576 20247-20258 SO_EXT:0000673 denotes transcripts
T9577 20281-20283 GO_EXT:reverse_transcription_or_reverse_transcriptase denotes RT
T9578 20293-20300 SO_EXT:0000112 denotes primers
T9579 20310-20314 SO_EXT:0000147 denotes exon
T9580 20342-20345 CHEBI_SO_EXT:RNA denotes RNA
T9581 20378-20384 UBERON:0000479 denotes tissue
T9582 20419-20421 GO_EXT:reverse_transcription_or_reverse_transcriptase denotes RT
T9583 20422-20433 SO_EXT:0000006 denotes PCR product
T9584 20439-20441 SO_EXT:0000028 denotes bp
T9585 20452-20461 SO_EXT:sequence_truncation_process denotes truncated
T9586 20462-20465 PR_EXT:000004122 denotes Apc
T9587 20467-20470 PR_EXT:000004122 denotes Apc
T9588 20476-20482 SO_EXT:0001023 denotes allele
T9589 20495-20502 UBERON:0000479 denotes tissues
T9590 20513-20524 GO_EXT:recombinase denotes recombinase
T9591 20540-20549 GO:0010467 denotes expressed
T9592 20557-20560 PR_EXT:000009454 denotes K14
T9593 20574-20578 NCBITaxon:10088 denotes mice
T9594 20633-20636 PR_EXT:000009454 denotes K14
T9595 20650-20655 NCBITaxon:10088 denotes mouse
T9596 20656-20663 UBERON:0000479 denotes tissues
T9597 20679-20684 UBERON:0002107 denotes liver
T9598 20688-20691 PR_EXT:000009454 denotes K14
T9599 20705-20709 NCBITaxon:10088 denotes mice
T9600 20741-20750 SO_EXT:wild_type_entity_or_quality denotes wild-type
T9601 20751-20757 SO_EXT:0001023 denotes allele
T9602 20763-20765 SO_EXT:0000028 denotes bp
T9603 20791-20794 CHEBI_SO_EXT:RNA denotes RNA
T9604 20841-20854 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T9605 20878-20884 UBERON:0000479 denotes tissue
T9606 20890-20898 SO_EXT:genotype_or_entity_with_genotype denotes genotype
T12344 20929-20932 PR_EXT:000009454 denotes K14
T12345 20944-20947 PR_EXT:000004122 denotes Apc
T12346 20970-20984 UBERON:0002073 denotes Hair Follicles
T12347 21000-21009 UBERON:0007376 denotes Epidermis
T12348 21059-21063 UBERON:0001037 denotes hair
T12349 21086-21093 SO_EXT:sequence_altered_entity denotes mutants
T12350 21175-21188 UBERON:0002073 denotes hair follicle
T12351 21195-21204 UBERON:0007376 denotes epidermal
T12352 21205-21214 UBERON:0004529 denotes appendage
T12353 21306-21310 UBERON:0001037 denotes hair
T12354 21324-21341 UBERON:0005942 denotes outer root sheath
T12355 21343-21346 UBERON:0005942 denotes ORS
T12356 21371-21384 CHEBI_EXT:biochemical denotes biochemically
T12357 21400-21414 _FRAGMENT denotes basal layer of
T12358 21419-21428 UBERON:0002025 denotes epidermis
T12359 21454-21467 UBERON:0002073 denotes hair follicle
T12360 21503-21520 UBERON:0005941 denotes inner root sheath
T12361 21552-21556 UBERON:0001037 denotes hair
T12362 21567-21572 CL_GO_EXT:cell denotes cells
T12363 21593-21606 UBERON:0002073 denotes hair follicle
T12364 21626-21644 UBERON:0005932 denotes hair follicle bulb
T12365 21669-21682 GO:0008283 denotes proliferating
T12366 21692-21697 CL_GO_EXT:cell denotes cells
T12367 21703-21716 GO_RO_EXT:developmental_differentiation_process denotes differentiate
T12368 21754-21771 UBERON:0005941 denotes inner root sheath
T12369 21780-21790 UBERON:0002074 denotes hair shaft
T12370 21815-21830 _FRAGMENT denotes anagen phase of
T12371 21835-21845 GO:0042640 denotes hair cycle
T12372 21835-21839 UBERON:0001037 denotes hair
T12373 21859-21873 UBERON:0002073 denotes hair follicles
T12374 21899-21903 NCBITaxon:10088 denotes mice
T12375 21904-21908 GO:0040007 denotes grew
T12376 21925-21941 UBERON:0002190 denotes subcutaneous fat
T12377 21938-21941 CHEBI_UBERON_EXT:triglyceride_or_adipose_tissue denotes fat
T12378 22035-22039 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12379 22077-22083 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12380 22084-22093 UBERON_EXT:follicle denotes follicles
T12381 22229-22235 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12382 22236-22240 NCBITaxon:10088 denotes mice
T12383 22261-22265 UBERON:0010166 denotes coat
T12384 22456-22466 UBERON_EXT:follicle denotes follicular
T12385 22518-22527 UBERON:0007376 denotes epidermis
T12386 22571-22580 UBERON_EXT:follicle denotes follicles
T12387 22627-22641 UBERON:0002073 denotes hair follicles
T12388 22653-22659 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12389 22660-22664 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12390 22846-22850 UBERON:0010166 denotes coat
T12391 22860-22866 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12392 22867-22871 NCBITaxon:10088 denotes mice
T12393 23777-23780 PR_EXT:000004122 denotes Apc
T12394 23786-23795 GO_EXT:regulator denotes regulator
T12395 23799-23808 PR_EXT:000002198 denotes β-catenin
T12396 23831-23844 GO:0016055 denotes Wnt signaling
T12397 23874-23884 GO:0010467 denotes expression
T12398 23888-23897 PR_EXT:000002198 denotes β-catenin
T12399 23914-23921 UBERON:0000479 denotes tissues
T12400 23937-23941 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12401 23943-23952 PR_EXT:000002198 denotes β-catenin
T12402 23970-23995 GO:0005912 denotes adherens junction complex
T12403 24014-24035 UBERON:0005942 denotes ORS of hair follicles
T12404 24040-24064 UBERON:0002025 denotes basal layer of epidermis
T12405 24072-24075 PR_EXT:000009454 denotes K14
T12406 24076-24086 GO:0010467 denotes expression
T12407 24136-24146 GO:0010467 denotes expression
T12408 24150-24152 PR_EXT:000009450 denotes K1
T12409 24154-24164 PR_EXT:000009167 denotes involucrin
T12410 24170-24178 PR_EXT:000009882 denotes loricrin
T12411 24180-24187 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes markers
T12412 24192-24199 _FRAGMENT denotes spinous
T12413 24213-24232 UBERON:0002026 denotes layers of epidermis
T12414 24204-24232 UBERON:0002069 denotes granular layers of epidermis
T12415 24268-24277 UBERON:0007376 denotes epidermis
T12416 24314-24324 GO:0010467 denotes expression
T12417 24328-24331 PR_EXT:000009454 denotes K14
T12418 24333-24335 PR_EXT:000009450 denotes K1
T12419 24337-24347 PR_EXT:000009167 denotes involucrin
T12420 24353-24361 PR_EXT:000009882 denotes loricrin
T12421 24366-24370 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12422 24376-24382 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12423 24405-24409 NCBITaxon:10088 denotes mice
T12424 24471-24486 GO_RO_EXT:developmental_differentiation_process denotes differentiation
T12425 24536-24546 GO:0010467 denotes expression
T12426 24550-24552 PR_EXT:keratin_6 denotes K6
T12427 24577-24586 GO:0010467 denotes expressed
T12428 24627-24633 _FRAGMENT denotes ORS of
T12429 24638-24651 UBERON:0005942 denotes hair follicle
T12430 24667-24676 UBERON:0007376 denotes epidermis
T12431 24756-24770 UBERON:0002073 denotes hair follicles
T12432 24783-24785 PR_EXT:keratin_6 denotes K6
T12433 24786-24798 GO_PATO_EXT:biological_localization_process_or_quality denotes localization
T12434 24874-24878 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12435 24880-24882 PR_EXT:keratin_6 denotes K6
T12436 24940-24943 UBERON:0005942 denotes ORS
T12437 24959-24967 GO_PATO_EXT:biological_localization_process_or_quality denotes localize
T12438 24983-24990 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes markers
T12439 24992-24995 PR_EXT:000009454 denotes K14
T12440 24999-25001 PR_EXT:000009481 denotes K5
T12441 25032-25036 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12442 25038-25051 GO:0008283 denotes proliferating
T12443 25052-25057 CL_GO_EXT:cell denotes cells
T12444 25086-25110 UBERON:0002025 denotes basal layer of epidermis
T12445 25129-25148 UBERON:0005932 denotes hair follicle bulbs
T12446 25181-25187 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12447 25188-25192 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12448 25201-25205 CHEBI:472552 denotes BrdU
T12449 25223-25227 PR_EXT:000010425 denotes Ki67
T12450 25228-25238 GO:0010467 denotes expression
T12451 25264-25269 CL_GO_EXT:cell denotes cells
T12452 25298-25311 UBERON:0002073 denotes hair follicle
T12453 25376-25382 _FRAGMENT denotes ORS of
T12454 25396-25410 UBERON:0005942 denotes hair follicles
T12455 25469-25487 UBERON:0005932 denotes hair follicle bulb
T12456 25499-25512 GO:0008283 denotes proliferating
T12457 25513-25518 CL_GO_EXT:cell denotes cells
T12458 25565-25571 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12459 25572-25576 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12460 25578-25591 GO:0008283 denotes proliferation
T12461 25654-25658 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12462 25703-25722 UBERON:0005932 denotes hair follicle bulbs
T12463 25759-25765 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12464 25766-25775 UBERON_EXT:follicle denotes follicles
T12465 25836-25842 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12466 25843-25847 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12467 25872-25880 GO:0016020 denotes membrane
T12468 25881-25886 CHEMINF_GO_EXT:chemical_binding_or_bond_formation denotes bound
T12469 25887-25899 GO_PATO_EXT:biological_localization_process_or_quality denotes localization
T12470 25917-25921 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12471 25923-25928 CL_GO_EXT:cell denotes cells
T12472 25941-25950 GO:0005829 denotes cytosolic
T12473 25951-25960 PR_EXT:000002198 denotes β-catenin
T12474 25961-25973 GO_PATO_EXT:biological_localization_process_or_quality denotes localization
T12475 26040-26049 PR_EXT:000002198 denotes β-catenin
T12476 26050-26060 GO:0010467 denotes expressing
T12477 26061-26066 CL_GO_EXT:cell denotes cells
T12478 26094-26107 GO:0008283 denotes proliferating
T12479 26108-26113 CL_GO_EXT:cell denotes cells
T12480 26226-26235 GO:0005829 denotes cytosolic
T12481 26236-26245 PR_EXT:000002198 denotes β-catenin
T12482 26285-26288 PR_EXT:000009454 denotes K14
T12483 26298-26300 PR_EXT:000009450 denotes K1
T12484 26310-26325 UBERON:0002025 denotes basal epidermis
T12485 26329-26332 PR_EXT:000009454 denotes K14
T12486 26342-26344 PR_EXT:keratin_6 denotes K6
T12487 26354-26359 _FRAGMENT denotes basal
T12488 26364-26369 CL:0000646 denotes cells
T12489 26360-26363 UBERON:0005942 denotes ORS
T12490 26360-26369 CL:0002561 denotes ORS cells
T12491 26364-26369 CL_GO_EXT:cell denotes cells
T12492 26393-26406 GO:0008283 denotes proliferating
T12493 26407-26412 CL_GO_EXT:cell denotes cells
T12494 26445-26458 UBERON:0002073 denotes hair follicle
T12495 26445-26472 GO:0031069 denotes hair follicle morphogenesis
T12496 26482-26489 SO_EXT:sequence_altered_entity denotes mutants
T12497 26507-26517 GO:0010467 denotes expression
T12498 26529-26543 PR_EXT:000014841 denotes Sonic hedgehog
T12499 26545-26548 PR_EXT:000014841 denotes Shh
T12500 26560-26569 GO:0010467 denotes expressed
T12501 26573-26583 UBERON:0005932 denotes hair bulbs
T12502 26587-26596 UBERON:0000922 denotes embryonic
T12503 26597-26601 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12504 26627-26640 UBERON:0002073 denotes hair follicle
T12505 26627-26654 GO:0031069 denotes hair follicle morphogenesis
T12506 26687-26693 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12507 26694-26703 UBERON:0000922 denotes embryonic
T12508 26704-26708 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12509 26733-26743 GO:0010467 denotes expression
T12510 26747-26750 PR_EXT:000014841 denotes Shh
T12511 26766-26775 UBERON:0007376 denotes epidermis
T12512 26813-26820 UBERON:0000922 denotes embryos
T12513 26900-26905 NCBITaxon:10088 denotes mouse
T12514 26906-26920 UBERON:0002073 denotes hair follicles
T12515 26993-26999 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12516 27000-27007 UBERON:0000922 denotes embryos
T12517 27112-27120 UBERON_EXT:follicle denotes follicle
T12518 27137-27140 PR_EXT:000014841 denotes Shh
T12519 27141-27151 GO:0010467 denotes expression
T12520 27196-27199 PR_EXT:000014841 denotes Shh
T12521 27235-27241 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12522 27242-27246 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12523 27266-27270 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12524 27308-27321 UBERON:0005086 denotes hair placodes
T12525 27335-27348 UBERON:0002073 denotes hair follicle
T12526 27335-27362 GO:0031069 denotes hair follicle morphogenesis
T12527 27407-27420 GO:0097617 denotes hybridization
T12528 27436-27442 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12529 27443-27450 UBERON:0000922 denotes embryos
T12530 27455-27464 PR_EXT:000002198 denotes β-catenin
T12531 27490-27500 GO:0010467 denotes expression
T12532 27512-27521 PR_EXT:000002198 denotes β-catenin
T12533 27525-27532 UBERON:0000922 denotes embryos
T12534 27589-27602 UBERON:0005086 denotes hair placodes
T12535 27617-27626 UBERON:0000922 denotes embryonic
T12536 27627-27631 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12537 27670-27680 GO_PATO_EXT:biological_patterning_process_or_quality denotes patterning
T12538 27728-27741 UBERON:0005086 denotes hair placodes
T12539 27760-27766 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12540 27767-27776 UBERON:0000922 denotes embryonic
T12541 27777-27781 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12542 27805-27818 UBERON:0005086 denotes hair placodes
T12543 27852-27856 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12544 27868-27873 UBERON:0002101 denotes limbs
T12545 27883-27890 SO_EXT:sequence_altered_entity denotes mutants
T12546 27933-27940 UBERON:0000922 denotes embryos
T12547 28000-28006 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12548 28007-28015 UBERON:0013623 denotes footpads
T12549 28023-28036 UBERON:0005086 denotes hair placodes
T12550 28122-28135 UBERON:0005086 denotes hair placodes
T12551 28157-28165 UBERON:0013623 denotes footpads
T12552 28199-28212 UBERON:0005086 denotes hair placodes
T12553 28235-28238 PR_EXT:000004122 denotes Apc
T12554 28239-28243 SO_EXT:0000704 denotes gene
T12555 28974-28989 GO_RO_EXT:developmental_differentiation_process denotes differentiation
T12556 29022-29028 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12557 29029-29033 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T12558 29053-29062 UBERON:0000922 denotes embryonic
T12559 29053-29062 _FRAGMENT denotes embryonic
T12560 29077-29090 GO:0048598 denotes morphogenesis
T12561 29063-29076 UBERON:0002073 denotes hair follicle
T12562 29063-29090 GO:0031069 denotes hair follicle morphogenesis
T12563 29150-29163 UBERON:0002073 denotes hair follicle
T12564 29150-29177 GO:0031069 denotes hair follicle morphogenesis
T12565 29185-29190 GO:0007567 denotes natal
T12566 29191-29197 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T12567 29198-29202 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T14438 29216-29219 PR_EXT:000009454 denotes K14
T14439 29239-29242 PR_EXT:000004122 denotes Apc
T14440 29252-29261 UBERON:0007376 denotes Epidermal
T14441 29262-29272 UBERON:0004529 denotes Appendages
T14442 29288-29295 CHEBI_GO_EXT:biological_process_or_quality_or_role denotes biology
T14443 29299-29313 UBERON:0002073 denotes hair follicles
T14444 29315-29318 PR_EXT:000009454 denotes K14
T14445 29338-29341 PR_EXT:000004122 denotes Apc
T14446 29381-29390 UBERON:0007376 denotes epidermal
T14447 29391-29401 UBERON:0004529 denotes appendages
T14448 29417-29427 UBERON:0000483 denotes epithelial
T14449 29428-29439 UBERON:0003104 denotes mesenchymal
T14450 29505-29511 UBERON:0001091 denotes dental
T14451 29538-29543 UBERON:0001091 denotes Tooth
T14452 29617-29629 UBERON:0000924 denotes ectodermally
T14453 29638-29653 UBERON:0002424 denotes oral epithelium
T14454 29674-29713 UBERON:0007213 denotes cranial neural crest–derived mesenchyme
T14455 29728-29733 UBERON:0001091 denotes tooth
T14456 29760-29765 UBERON:0001091 denotes tooth
T14457 29786-29793 SO_EXT:sequence_altered_entity denotes mutants
T14458 29826-29839 UBERON:0000167 denotes oral cavities
T14459 29875-29885 UBERON:0008281 denotes tooth buds
T14460 29919-29924 UBERON:0001091 denotes teeth
T14461 29945-29949 GO:0040007 denotes grow
T14462 29989-29993 UBERON:0001913 denotes milk
T14463 30003-30007 CHEBI_EXT:33290 denotes food
T14464 30026-30036 GO:0010467 denotes expression
T14465 30049-30052 PR_EXT:000009454 denotes K14
T14466 30057-30066 PR_EXT:000002198 denotes β-catenin
T14467 30081-30085 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T14468 30095-30103 GO:0016020 denotes membrane
T14469 30104-30109 CHEMINF_GO_EXT:chemical_binding_or_bond_formation denotes bound
T14470 30110-30120 GO:0010467 denotes expression
T14471 30124-30133 PR_EXT:000002198 denotes β-catenin
T14472 30150-30153 PR_EXT:000009454 denotes K14
T14473 30154-30164 GO:0010467 denotes expressing
T14474 30165-30180 UBERON:0002424 denotes oral epithelium
T14475 30185-30196 CL:0000059 denotes ameloblasts
T14476 30207-30211 NCBITaxon:10088 denotes mice
T14477 30216-30223 SO_EXT:sequence_altered_entity denotes mutants
T14478 30237-30240 PR_EXT:000009454 denotes K14
T14479 30241-30251 GO:0010467 denotes expressing
T14480 30252-30257 CL_GO_EXT:cell denotes cells
T14481 30277-30286 GO:0005829 denotes cytosolic
T14482 30287-30294 GO:0005634 denotes nuclear
T14483 30295-30304 PR_EXT:000002198 denotes β-catenin
T14484 30334-30340 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T14485 30341-30345 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T14486 30394-30404 UBERON:0008281 denotes tooth buds
T14487 30412-30418 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T14488 30419-30423 NCBITaxon:10088 denotes mice
T14489 30462-30465 PR_EXT:000014841 denotes Shh
T14490 30466-30476 GO:0010467 denotes expression
T14491 30493-30506 UBERON:0007115 denotes primary teeth
T14492 30533-30536 PR_EXT:000004122 denotes Apc
T14493 30566-30584 UBERON:0006914 denotes squamous epithelia
T14494 30575-30594 UBERON:0001772 denotes epithelia of cornea
T14495 30575-30587 _FRAGMENT denotes epithelia of
T14496 30602-30610 _FRAGMENT denotes salivary
T14497 30626-30632 UBERON:0004809 denotes glands
T14498 30616-30632 UBERON:0004694 denotes Hardarian glands
T14499 30596-30600 _FRAGMENT denotes oral
T14500 30626-30632 UBERON:0010047 denotes glands
T14501 30676-30689 UBERON:0002073 denotes hair follicle
T14502 30715-30728 UBERON:0002073 denotes hair follicle
T14503 30715-30742 GO:0031069 denotes hair follicle morphogenesis
T14504 30770-30779 UBERON:0000483 denotes epithelia
T17003 30782-30785 PR_EXT:000009454 denotes K14
T17004 30797-30800 PR_EXT:000004122 denotes Apc
T17005 30830-30836 UBERON:0002370 denotes thymic
T17006 30837-30841 NCBITaxon:10088 denotes Mice
T17007 30842-30848 UBERON:0002370 denotes Thymus
T17008 30855-30860 UBERON:0000062 denotes organ
T17009 30888-30891 PR_EXT:000009454 denotes K14
T17010 30892-30902 GO:0010467 denotes expression
T17011 30935-30943 CL_UBERON_EXT:lymphocyte_or_lymphoid_progenitor_or_system_or_tissue denotes lymphoid
T17012 30944-30949 UBERON:0000062 denotes organ
T17013 30954-30963 CL:0000893 denotes thymocyte
T17014 31014-31028 CL:0002364 denotes TECs of cortex
T17015 31014-31021 _FRAGMENT denotes TECs of
T17016 31033-31040 CL:0002365 denotes medulla
T17017 31022-31028 UBERON:0001851 denotes cortex
T17018 31033-31040 UBERON:0000958 denotes medulla
T17019 31084-31092 UBERON:0001851 denotes Cortical
T17020 31084-31092 _FRAGMENT denotes Cortical
T17021 31107-31110 CL:0002364 denotes TEC
T17022 31097-31106 UBERON:0000958 denotes medullary
T17023 31097-31110 CL:0002365 denotes medullary TEC
T17024 31153-31163 GO:0010467 denotes expression
T17025 31189-31191 PR_EXT:000009495 denotes K8
T17026 31193-31196 PR_EXT:000009458 denotes K18
T17027 31198-31200 PR_EXT:000009481 denotes K5
T17028 31206-31209 PR_EXT:000009454 denotes K14
T17029 31222-31228 UBERON:0002370 denotes thymus
T17030 31244-31252 CL_UBERON_EXT:lymphocyte_or_lymphoid_progenitor_or_system_or_tissue denotes lymphoid
T17031 31253-31258 UBERON:0000062 denotes organ
T17032 31265-31271 UBERON:0009911 denotes lobule
T17033 31305-31308 CL:0002293 denotes TEC
T17034 31332-31338 UBERON:0001851 denotes cortex
T17035 31352-31359 UBERON:0000958 denotes medulla
T17036 31424-31430 UBERON:0002370 denotes thymus
T17037 31512-31513 CHEBI:51686 denotes H
T17038 31514-31515 CHEBI_EXT:eosin denotes E
T17039 31528-31534 UBERON:0002370 denotes thymus
T17040 31540-31546 UBERON:0001851 denotes cortex
T17041 31567-31575 CL_UBERON_EXT:lymphocyte_or_lymphoid_progenitor_or_system_or_tissue denotes lymphoid
T17042 31567-31582 UBERON:0001744 denotes lymphoid tissue
T17043 31625-31631 UBERON:0003891 denotes stroma
T17044 31639-31646 UBERON:0000958 denotes medulla
T17045 31680-31691 CL:0000542 denotes lymphocytes
T17046 31701-31707 UBERON:0001851 denotes cortex
T17047 31713-31720 UBERON:0000958 denotes medulla
T17048 31751-31757 UBERON:0001851 denotes cortex
T17049 31769-31773 NCBITaxon:10088 denotes mice
T17050 31779-31785 UBERON:0002370 denotes thymus
T17051 31819-31824 UBERON:0007023 denotes adult
T17052 31833-31842 GO:0060033 denotes regresses
T17053 31886-31890 NCBITaxon:10088 denotes mice
T17054 31932-31942 CL:0000893 denotes thymocytes
T17055 31948-31959 GO:0007067 denotes mitotically
T17056 31974-31980 UBERON:0001851 denotes cortex
T17057 31998-32002 CHEBI:472552 denotes BrdU
T17058 32062-32068 UBERON:0002370 denotes thymus
T17059 32084-32088 NCBITaxon:10088 denotes mice
T17060 32127-32130 PR_EXT:000009454 denotes K14
T17061 32143-32153 GO:0010467 denotes expression
T17062 32194-32198 CL:0002293 denotes TECs
T17063 32212-32221 UBERON:0000958 denotes medullary
T17064 32240-32253 CL:0000312 denotes keratinocytes
T17065 32257-32277 UBERON:0003987 denotes Hassall's corpuscles
T17066 32299-32310 GO:0005737 denotes cytoplasmic
T17067 32324-32333 PR_EXT:000002198 denotes β-catenin
T17068 32359-32368 UBERON:0000958 denotes medullary
T17069 32369-32379 UBERON:0000483 denotes epithelial
T17070 32369-32385 CL:0000066 denotes epithelial cells
T17071 32380-32385 CL_GO_EXT:cell denotes cells
T17072 32414-32417 PR_EXT:000009454 denotes K14
T17073 32418-32428 GO:0010467 denotes expression
T17074 32451-32453 PR_EXT:000009495 denotes K8
T17075 32470-32480 UBERON:0000483 denotes epithelial
T17076 32470-32486 CL:0000066 denotes epithelial cells
T17077 32481-32486 CL_GO_EXT:cell denotes cells
T17078 32499-32506 UBERON:0000958 denotes medulla
T17079 32511-32517 UBERON:0001851 denotes cortex
T17080 32531-32533 PR_EXT:000009450 denotes K1
T17081 32569-32573 NCBITaxon:10088 denotes mice
T17082 32593-32597 NCBITaxon:10088 denotes mice
T17083 32617-32631 GO_PATO_RO_EXT:developmental_differentiation_process_or_quality denotes differentiated
T17084 32632-32645 CL:0000312 denotes keratinocytes
T17085 32657-32677 UBERON:0003987 denotes Hassall's corpuscles
T17086 33241-33247 UBERON:0002370 denotes thymus
T17087 33282-33289 SO_EXT:sequence_altered_entity denotes mutants
T17088 33314-33320 UBERON:0002370 denotes thymus
T17089 33337-33344 UBERON:0009911 denotes lobules
T17090 33362-33366 NCBITaxon:10088 denotes mice
T17091 33375-33381 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17092 33382-33388 UBERON:0002370 denotes thymus
T17093 33534-33540 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17094 33541-33545 NCBITaxon_UBERON_EXT:pup denotes pups
T17095 33626-33632 UBERON:0002370 denotes thymus
T17096 33642-33648 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17097 33649-33652 NCBITaxon_UBERON_EXT:pup denotes pup
T17098 33700-33704 UBERON_EXT:body denotes body
T17099 33768-33774 UBERON:0002370 denotes thymus
T17100 33829-33835 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17101 33889-33895 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17102 33896-33902 UBERON:0002370 denotes thymus
T17103 34001-34011 UBERON:0000483 denotes epithelial
T17104 34028-34034 UBERON:0002370 denotes thymus
T17105 34099-34109 CL:0000893 denotes thymocytes
T17106 34125-34131 UBERON:0001851 denotes cortex
T17107 34159-34173 _FRAGMENT denotes populations of
T17108 34190-34195 UBERON_EXT:cell_clump_or_cluster_or_group_or_mass_or_population denotes cells
T17109 34190-34195 CL_GO_EXT:cell denotes cells
T17110 34199-34200 CHEBI:51686 denotes H
T17111 34201-34202 CHEBI_EXT:eosin denotes E
T17112 34240-34246 UBERON:0001851 denotes cortex
T17113 34261-34268 UBERON:0000958 denotes medulla
T17114 34292-34297 CL_GO_EXT:cell denotes cells
T17115 34313-34320 GO:0005634 denotes nuclear
T17116 34321-34330 PR_EXT:000002198 denotes β-catenin
T17117 34364-34373 UBERON:0000958 denotes medullary
T17118 34374-34379 CL_GO_EXT:cell denotes cells
T17119 34395-34404 PR_EXT:000002198 denotes β-catenin
T17120 34466-34478 GO_PATO_EXT:biological_localization_process_or_quality denotes Localization
T17121 34482-34485 PR_EXT:000009454 denotes K14
T17122 34507-34512 CL_GO_EXT:cell denotes cells
T17123 34520-34527 UBERON:0000958 denotes medulla
T17124 34553-34555 PR_EXT:000009495 denotes K8
T17125 34556-34568 GO_PATO_EXT:biological_localization_process_or_quality denotes localization
T17126 34598-34604 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17127 34605-34611 UBERON:0002370 denotes thymus
T17128 34625-34642 UBERON:0003846 denotes thymic epithelial
T17129 34698-34709 CL:0000542 denotes lymphocytes
T17130 34774-34787 GO_PATO_EXT:cell_proliferation_or_proliferativity denotes Proliferative
T17131 34826-34836 CL:0000893 denotes thymocytes
T17132 34869-34875 UBERON:0002370 denotes thymus
T17133 34885-34895 UBERON:0000483 denotes epithelial
T17134 34885-34901 CL:0000066 denotes epithelial cells
T17135 34896-34901 CL_GO_EXT:cell denotes cells
T17136 34987-34993 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17137 34994-34999 UBERON:0002370 denotes thymi
T17138 35015-35021 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17139 35022-35028 UBERON:0002370 denotes thymus
T17140 35046-35049 PR_EXT:000009454 denotes K14
T17141 35050-35060 GO:0010467 denotes expression
T17142 35082-35084 PR_EXT:000009495 denotes K8
T17143 35085-35095 GO:0010467 denotes expression
T17144 35115-35120 CL_GO_EXT:cell denotes cells
T17145 35136-35147 CL:0000646 denotes basal cells
T17146 35142-35147 CL_GO_EXT:cell denotes cells
T17147 35155-35159 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T17148 35165-35169 CL:0002293 denotes TECs
T17149 35217-35222 CL_GO_EXT:cell denotes cells
T17150 35248-35255 GO:0005634 denotes nuclear
T17151 35260-35271 GO:0005737 denotes cytoplasmic
T17152 35272-35281 PR_EXT:000002198 denotes β-catenin
T17153 35308-35315 GO:0005634 denotes nuclear
T17154 35328-35337 PR_EXT:000002198 denotes β-catenin
T17155 35381-35387 UBERON:0002370 denotes thymus
T17156 35419-35422 PR_EXT:000009454 denotes K14
T17157 35427-35436 PR_EXT:000002198 denotes β-catenin
T17158 35515-35521 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17159 35522-35528 UBERON:0002370 denotes thymus
T17160 35560-35579 UBERON:0003987 denotes Hassall's corpuscle
T17161 35615-35618 PR_EXT:000009454 denotes K14
T17162 35624-35626 PR_EXT:000009495 denotes K8
T17163 35627-35637 GO:0010467 denotes expressing
T17164 35638-35650 GO:0031424 denotes keratinizing
T17165 35638-35650 _FRAGMENT denotes keratinizing
T17166 35662-35667 CL:0000311 denotes cells
T17167 35651-35661 UBERON:0000483 denotes epithelial
T17168 35651-35667 CL:0000066 denotes epithelial cells
T17169 35662-35667 CL_GO_EXT:cell denotes cells
T17170 35743-35754 CL:0000775 denotes neutrophils
T17171 35759-35770 CL:0000235 denotes macrophages
T17172 35788-35794 UBERON:0002370 denotes thymus
T17173 35798-35806 GO_EXT:reaction_or_response denotes response
T17174 35899-35914 GO_RO_EXT:developmental_differentiation_process denotes differentiation
T17175 35924-35931 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes markers
T17176 35956-35960 NCBITaxon:10088 denotes mice
T17177 35975-35977 PR_EXT:000009450 denotes K1
T17178 35982-35992 PR_EXT:000009167 denotes involucrin
T17179 36027-36047 UBERON:0003987 denotes Hassall's corpuscles
T17180 36071-36077 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17181 36078-36083 UBERON:0002370 denotes thymi
T17182 36106-36110 NCBITaxon:10088 denotes mice
T17183 36114-36124 CL:0000893 denotes thymocytes
T17184 36142-36146 CHEBI:472552 denotes BrdU
T17185 36191-36203 GO:0031424 denotes keratinizing
T17186 36191-36203 _FRAGMENT denotes keratinizing
T17187 36215-36220 CL:0000311 denotes cells
T17188 36204-36214 UBERON:0000483 denotes epithelial
T17189 36204-36220 CL:0000066 denotes epithelial cells
T17190 36215-36220 CL_GO_EXT:cell denotes cells
T17191 36272-36276 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T17192 36302-36312 GO:0010467 denotes expression
T17193 36316-36325 PR_EXT:000002198 denotes β-catenin
T17194 36352-36362 UBERON:0000483 denotes epithelial
T17195 36352-36368 CL:0000066 denotes epithelial cells
T17196 36363-36368 CL_GO_EXT:cell denotes cells
T17197 36392-36397 CL_GO_EXT:cell denotes cells
T17198 36416-36423 GO:0005634 denotes nuclear
T17199 36424-36433 PR_EXT:000002198 denotes β-catenin
T17200 36474-36480 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17201 36481-36485 NCBITaxon:10088 denotes mice
T17202 36496-36503 GO:0005634 denotes nuclear
T17203 36504-36516 GO_PATO_EXT:biological_localization_process_or_quality denotes localization
T17204 36520-36529 PR_EXT:000002198 denotes β-catenin
T17205 36551-36554 PR_EXT:000009454 denotes K14
T17206 36564-36569 CL_GO_EXT:cell denotes cells
T17207 36589-36603 GO_PATO_RO_EXT:developmental_differentiation_process_or_quality denotes differentiated
T17208 36604-36615 CL:0000646 denotes basal cells
T17209 36610-36615 CL_GO_EXT:cell denotes cells
T17210 36630-36634 NCBITaxon:10088 denotes mice
T17211 36667-36677 GO:0010467 denotes expression
T17212 36693-36699 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17213 36700-36706 UBERON:0002370 denotes thymus
T17214 36759-36768 PR_EXT:000002198 denotes β-catenin
T17215 36769-36779 GO:0010467 denotes expression
T17216 36826-36834 GO_PATO_EXT:biological_localization_process_or_quality denotes localize
T17217 36840-36842 PR_EXT:000009495 denotes K8
T17218 36843-36846 PR_EXT:000009454 denotes K14
T17219 36847-36857 GO:0010467 denotes expression
T17220 36911-36916 CL_GO_EXT:cell denotes cells
T17221 36930-36936 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T17222 36937-36943 UBERON:0002370 denotes thymus
T17223 36994-36997 PR_EXT:000004122 denotes Apc
T17224 37030-37039 PR_EXT:000002198 denotes β-catenin
T17225 37043-37046 PR_EXT:000009454 denotes K14
T17226 37047-37057 GO:0010467 denotes expressing
T17227 37058-37062 CL:0002293 denotes TECs
T17228 37086-37099 GO:0008283 denotes proliferation
T17229 37104-37136 GO:0030216 denotes differentiation to keratinocytes
T17230 37123-37136 CL:0000312 denotes keratinocytes
T17231 37202-37211 UBERON:0000958 denotes medullary
T17232 37202-37211 _FRAGMENT denotes medullary
T17233 37224-37228 CL:0002365 denotes TECs
T17234 37215-37223 UBERON:0001851 denotes cortical
T17235 37215-37228 CL:0002364 denotes cortical TECs
T17236 37245-37248 CL:0002293 denotes TEC
T17237 37295-37305 CL:0000893 denotes thymocytes
T17238 37310-37320 GO_PATO_EXT:biological_maturation denotes maturation
T17239 37329-37333 NCBITaxon:10088 denotes mice
T17240 37342-37348 UBERON:0002370 denotes thymic
T19004 0-37367 PR_EXT:000004122 denotes Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus Role of APC in Skin and Its Appendages Abstract The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre–mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; ApcCKO/CKO mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial–mesenchymal interactions for their development. Synopsis Patients with familial adenomatous polyposis (FAP) and its variant, Gardner's syndrome, will develop hundreds of colorectal polyps. It is a heritable disease that is linked to a genetic mutation in the tumor suppressor gene APC (adenomatous polyposis coli). These individuals also develop extracolonic symptoms, among which are congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, epidermoid cysts, disorders of the maxillary and skeletal bones, and dental abnormalities, suggesting the importance of APC functions in these organs. To understand the role of Apc in development and in organs other than intestine, we generated Apc mutant mice that can conditionally delete the gene when exposed to Cre recombinase. These mice were mated with K14 (Keratin 14)–cre mice that express Cre recombinase in skin and its appendages. The authors found that the mutant mice that have lost Apc in K14-cre transgene–expressing tissues were viable, but had stunted growth and died before weaning. These mutant mice showed developmental abnormalities not only in skin but also in many epithelial-derived tissues, including teeth and thymus. This work demonstrates the importance of Apc in development of many organs, and provides new insights into diagnosis and management of patients with APC mutations. Introduction Adenomatous polyposis coli (APC) is a member of the Wnt signaling pathway and one of its known functions is to regulate the levels of β-catenin. Alterations in β-catenin regulation are very common in human tumors [1]. Loss of APC is associated with stabilization of the cytosolic β-catenin that ultimately results in its migration to the nucleus and activating a cascade of events leading to tumorigenesis. APC also interacts with a multitude of other cellular proteins, including axin-2 (AXIN2), plakoglobin (JUP), Asef (ARHGEF4), kinesin superfamily–associated protein 3 (KIFAP3), EB1 (MAPRE1), microtubules, and the human homolog of Drosophila discs large (DLG1). These interactions suggest that APC can potentially regulate many cellular functions, including intercellular adhesion, cytoskeletal organization, regulation of plakoglobin levels, regulation of the cell cycle and apoptosis, orientation of asymmetric stem cell division, and control of cell polarization [2,3]. APC is a tumor suppressor gene. Somatic mutations in APC are frequently found in many sporadic tumors of the colon and rectum. Autosomal dominant germline mutations in APC cause familial adenomatous polypois (FAP) and its variant, Gardner syndrome. FAP patients are characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer in the third and fourth decades of life [4,5]. In addition to colorectal neoplams, these individuals can develop extracolonic symptoms, among which are upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, disorders of the maxillary and skeletal bones, and dental abnormalities [6], suggesting the importance of APC gene functions in these organ systems. Although the role of APC in the initiation of human colorectal cancer is well established, its role in other tissue and developmental processes are not well understood. Given the importance of regulation of Wnt signaling in embryonic pattern formation and morphogenesis of many organs, mechanistic understanding of APC in development and in extracolonic tissues becomes critical to better assess potential adverse events in humans. One approach to understand the role of Apc in development is to develop mice with an inactivating Apc mutation. Several genetically modified mouse strains for Apc have been described [7–10]. Most of these models, in the heterozygous state, show a gastrointestinal and other tumor predisposition phenotype [7–10]. Mouse embryos that are homozygous for the genetic modification die during embryogenesis, and some of the models do not survive beyond gastrulation [8,11]. An alternate approach to understand the role of Apc in development and/or in specific tissues is to generate a mouse strain that carries a conditionally modified allele and mate it with a mouse strain that facilitates the modification of the conditional allele in specific cell lineages. To assess the role of Apc in different stages of life systematically, we generated mice containing a conditional knockout (CKO) mutant allele of Apc (ApcCKO). These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. We report here that K14 promoter-driven loss of Apc resulted in aberrant development of several organs that require inductive epithelial–mesenchymal interactions, including hair follicle, teeth, and thymus, and resulted in neonatal death in mice. We found that Apc plays a crucial role in determinations of cell fates during the embryonic development, possibly via temporal and tissue-specific regulation of β-catenin levels in the skin, its appendages, and in the thymus. Results Generation of the ApcCKO and ApcΔ580 Mice To investigate the role of Apc in development of skin and its appendages, we used the Cre/loxP technology to introduce a conditional mutation of the Apc gene in mice. We constructed embryonic stem (ES) cells and mice carrying an Apc allele harboring both a pair of loxP sites flanking Apc exon 14 and a pair of FLP recognition target (FRT) sites flanking PGK-neomycin selection cassette by recombineering [12,13] (Figure 1A, ApcCKON allele, N for neomycin cassette). A PGK-neomycin cassette was inserted in the same transcriptional orientation as Apc in intron 14 of the endogenous gene. The loxP and FRT sites were used to aid unidirectional recombination [12,13]. Two mouse lines containing the same modification were generated from two independent ES clones to ensure that these two lines behave in the same way. These ApcCKON/+ mice were crossed with FLPe-deleter to generate ApcCKO/+ mice that were heterozygous for the final Apc conditional (ApcCKO) allele that removed the PGK-neomycin cassette and contains only the loxP sites in the introns flanking exon 14. To assess the effect of deleting exon 14 in mice, both lines of ApcCKO/+ mice were crossed with the Cre-deleter to generate the germline knockout line of Apc, designated ApcΔ580/+. The mutant allele (ApcΔ580) lacks exon 14 (Figure 1A). The transcript from loss of exon 14 results in a shift in the normal reading frame, resulting in a premature chain termination codon which, if utilized, would result in a truncated polypeptide that is 605 aa in length, of which the first 580 aa correspond to the normal Apc protein. Figure 1 Generation of the Conditional Apc Allele (A) Schematic diagram of exons 14 and 15 of the mouse Apc gene, the targeting vector, and the resulting conditional allele with 2 LoxP sites sandwiching the exon 14. The PGK-neomycin cassette was inserted within intron 14 by recombineering technique. This cassette is sandwiched by 2 FRT sites that could be removed by crossing to FLPe-expressing mice. Positions of PCR primers used for genotyping PCR (F2, R2, R4) and RT-PCR (F546 and R721) are indicated. Positions of probe used for Southern blot analysis with NdeI sites are also shown. Upon Cre-mediated recombination, exon 14 is removed and leads to truncated Apc protein, of which the first 580 aa correspond to the normal. (B) Southern blot analysis of NdeI-digested genomic tail DNA isolated from F1 mice of various Apc mouse lines (ApcCKON, ApcΔ580), hybridized to a 600-bp probe. Tail genomic DNA from ApcCKON F1 mice derived from a modified ES clone showed a 12-kb band for the ApcCKON allele and a 10-kb band for the wild-type allele, whereas genomic DNA from the ApcΔ580 mouse was heterozygous for the ApcΔ580 allele (9.2-kb band). (C) Kaplan-Meier survival plot of ApcCKO/+ mice (thin solid line, n = 39), ApcCKO/CKO mice (thin dotted line, n = 57), ApcΔ580/+ mice (solid line, n = 51), and wild-type littermates (broken line, n = 21). Heterozygosity of the ApcΔ580 allele led to a significantly shortened survival (p < 0.0001), whereas those of heterozygous and homozygous ApcCKO mice had no significant difference to that of wild-type littermates. Southern blot analysis of tail DNA from F1 offspring of both ApcCKON and ApcΔ580 lines confirmed the germline transmission of modified Apc allele (Figure 1B). Mice that are heterozygous for ApcΔ580 mutation are viable but have a significantly reduced lifespan (Figure 1C). These results suggested that deletion of exon 14 indeed results in either loss or abnormal function of the Apc gene product. ApcΔ580/+ mice have median survival of 5 mo of age (Figure 1C), with progressive signs of rectal bleeding and anemia. Similar to the results reported with an independently generated ApcΔ580/+ conditional mouse strain [14], ApcΔ580/+ mice had more than 100 (120 ± 37, n = 11) intestinal tumors at the time of their death (Figure S1). Inactivation of wild-type Apc is an important prerequisite for tumor development. We analyzed 30 intestinal tumors from ApcΔ580/+ mice by in vitro transcription and translation assay, but none of them showed truncated Apc products (unpublished data), indicating that the most likely mechanism of wild-type Apc inactivation is by allelic loss. The mutant allele had to be maintained and transmitted through male mice, as ApcΔ580/+ females were frequently not healthy enough to successfully nurse their own pups because of their tumor burden. ApcCKO/+ mice were intercrossed to generate ApcCKO/CKO offspring. Approximately one-quarter of the offspring (17 of 81) were homozygous for the ApcCKO allele. These mice as well as heterozygous mice for ApcCKO allele are normal, showing no differences in their survival to the wild-type littermates (Figure 1C). We tested whether our ApcCKO allele can compliment the wild-type allele by crossing the ApcCKO/CKO female with ApcΔ580/+ male mouse. The resultant ApcCKO/Δ580 offspring were viable and born in the Mendelian ratio, suggesting that the presence of loxP sites in introns flanking exon 14 have no adverse effect on the function of the Apc gene. K14-Driven Loss of Apc Results in Severe Growth Retardation and Early Lethality To introduce the mutation of Apc into cells expressing K14, we crossed WW6 ES cell–derived [15] ApcCKO/+ mice with K14-cre recombinase mice in FVB background [16]. The K14-cre; ApcCKO/+ mice were normal in appearance and were fertile. K14-cre; ApcCKO/+ males were crossed to ApcCKO/CKO females to avoid the potential deleter effect in oocytes of K14-cre–positive females [17]. The mice were intercrossed thereafter for maintenance; hence, the mice used for analysis were in a mixed background of FVB, 129/S, and C57BL/6 in similar proportions, with minimal contribution of SJ. The K14 promoter is a commonly used epidermal cell promoter because of its expression by the mitotically active cells of the epidermis and its appendages in mature skin [18], but most notably it is active in embryonic ectoderm as early as the single layered ectodermal stage of embryonic day (E) 9.5 [19]. A restricted expression of K14 is also found in thymic epithelial cells (TECs) in the medulla of normal thymus [20]. We genotyped a total of 458 pups (8–10 d old) from 67 litters resulting from crosses between K14-cre; ApcCKO/+ and ApcCKO/CKO mice. The mutant mice of the genotype K14-cre; ApcCKO/CKO (hereafter, KA mutant) were born, but the observed frequency of KA mutants was much less than expected (78 of 458 [17.0%]; p < 0.0005 Chi-square analysis, Table 1). To assess the basis for the neonatal lethality of KA mutants, we monitored three litters from birth to weaning by measuring the body weight of each pup every day. A total of 25 pups were born from three litters, of which 7 (28%) were confirmed to be K14-cre; ApcCKO/CKO by genotyping, indicating that KA mutants were born in the expected Mendelian ratio. The KA mutant pups were nursed normally, and there was milk in their stomachs during the first 2 or 3 d after birth, but they failed to thrive (Figure 2). By postnatal day (P) 8–10, at the time of genotyping, many KA mutant pups were considerably smaller than their littermates (Figure 2B–2F) and some have died at or prior to this age. None of KA mutants survived to weaning age. Table 1 Genotype Distribution of Progeny from the Matings Figure 2 Postnatal Mortality and Stunted Growth in K14-cre; ApcCKO/CKO Mutant Mice Animals whose genotype is either heterozygous or homozygous for the wild-type Apc allele are referred to as normal (N); those whose genotype are K14-cre; ApcCKO/CKO and show the presence of K14-cre–recombined mutant Apc allele are called mutant (M). (A) Two P3 mutant mice, M1 and M2, and their normal littermates, showing size variation among mutants. (B) P8 mutant mouse (right) and a normal littermate. Note sparseness of hair coat and abnormal ears. (C–D) Vibrissae of whisker pads are short and oddly angled in a P12 mutant mouse (C), relative to control (D). Note the lack of incisors in the mutant. (E) A P17 mutant mouse (right) with its littermate. Its bare forehead, dorsal median line, and abnormal ears are evident. (F) Growth curve of mutants and normal littermates. Mutants exhibit stunted growth, which became more prominent as they aged, and weigh significantly less than littermates from P8 (p < 0.05). (G) Comparison of mutant and normal thymus from P3 mice. The mutant thymus (left) is dramatically smaller for its age compared to the normal littermate (right). The scale bar equals 1 mm. (H) Skeletal preparations of normal (left) and mutant (right), showing differences in development of both incisor (I) and molar (M) teeth. The ability of whole embryos to exclude blue dye was used to examine the epidermal barrier, normally acquired beginning at E16 and complete by E18.5 [21]. Analyses of E17.5–E18.5 KA mutants showed that they were able to exclude blue dye, indicating that the epidermal barrier was intact (Figure S2). At these embryonic ages, there were no differences in size between the mutants and their littermates, but the mutants showed a patch of “birthmark” or dark pigmentation on their foreheads and a dark median line that ran caudally from head to tail. Their external ears or pinnae were shriveled in appearance and pigmented compared to those of littermates. External characteristics of KA mutants that were evident at E18.5 persisted after birth and became more prominent as they grew (Figure 2A–2F). Growth of pelage hair was generally delayed in the mutants. At around P8, the KA mutants were hairless and had wrinkled skin while their phenotypically normal littermates had a smooth thin coat of hair (Figure 2B). At this age, two lower incisors start to erupt in normal littermates and these were absent in the KA mutants (Figure 2C and 2D). Animals also tended to be smaller and around P10–P12 displayed abnormally short and misshapen vibrissae and short, shaggy pelage hairs (Figure 2C and 2D). Development of thick ridges in their skin, particularly around the ears, eyelids, forehead, nose, and paws, became noticeable (Figure 2E). These regions looked scaly, and these animals hardly kept their eyes open. In contrast to the normal littermates that consistently increased their body weight with age, surviving KA mutants started to lose weight from P10 onwards; by P16–P17 they were all lethargic, and none of them survived to weaning (Figure 2E and 2F). At the time of autopsy all the mutants were toothless, without incisors or molars, and their stomachs were consistently small and had no solid food, unlike their age-matched littermates, suggesting that the observed weight loss could be the result of failure to ingest solid food (Figure 2F). Interestingly, changes in body weights and timing of hair growth varied considerably among mutant pups even if they were from the same litter, whereas those of phenotypically normal littermates tended to be similar. This difference was also reflected in the variation in timing of death in mutants: some mutant pups were born alive but died within a day or two, some survived close to the weaning age. This variability of the mutant phenotypes suggests possible variation in the timing and efficiency of cre-mediated Apc deletion. It is possible that the genetic background has a role to play in this variability. Gross examination of internal organs also showed that the mutants' thymi were consistently inconspicuous and were very small for their age, whereas those of their littermates were very prominent in size (Figure 2G). This difference was evident as early as P3. Quite frequently mutant thymi in P12–P17 mutant mice also contained black deposits within the tissue (unpublished data). Mutant mice were also examined for any skeletal abnormalities by preparing skeletal specimens of P16–P17 mice stained with Alizarin red. No differences between the normal and KA mutant mice in the mandibular bone can be detected, but the mutant mice lacked or had underdeveloped set of maxillary incisors and molars (Figure 2H). We detected no other major skeletal abnormalities. Genotype- and Tissue-Specific Expression of the Truncated Apc Transcripts To assess the molecular effects of the K14-cre–mediated recombination, we screened for the presence of deleted Apc (ApcΔ580) alleles. Genomic DNA was extracted from liver, thymus, and skin from all 4 possible genotypes: K14-cre; ApcCKO/CKO, K14-cre; ApcCKO/+, ApcCKO/CKO, and ApcCKO/+. Genotyping on genomic DNA from these tissues showed that the ApcΔ580 allele (500-bp product) was detected only from the skin and thymus of the K14-cre–positive mice. The presence of mutant Apc allele in the thymus of K14-cre; ApcCKO/+ mice was consistently much less than the DNA from the skin of the same animal or other tissues from the KA mutants. In addition, this product was not detected at all in either the liver of K14-cre–positive or in any of the K14-cre–negative mouse tissues samples, establishing that Cre-mediated recombination has taken place in the tissue-specific manner in the mice that inherited K14-cre (Figure 3A). Figure 3 Tissue-Specific Detection and Expression of Deleted Apc Alleles (A) Tissue-specific genotyping PCR. Only genomic DNA samples from the skin (S) and thymus (T), but not liver (L) of mice positive for K14-cre show the presence of deleted ApcΔ580 allele. (B) Genotype- and tissue-specific expression of the truncated Apc transcripts. A representative gel of RT-PCR using primers F546 and R721, showing that only RNA from the skin and thymus but not liver of mice positive for K14-cre have transcripts from both wild-type (528 bp) and deleted (313 bp) Apc alleles. Apc transcripts were also analyzed by RT-PCR with primers spanning exon 14 (Figure 1A) using total RNA isolated from the corresponding tissue samples. We detected the expected RT-PCR product (313 bp) from the truncated Apc (ApcΔ580) allele only in the tissues where Cre recombinase is known to be expressed in the K14-cre–positive mice. However, this product was not detected in either the K14-cre–negative mouse tissues samples or the liver of K14-cre–positive mice, and only the product from the wild-type allele (528 bp) was detected from these RNA samples, further confirming that Cre-mediated recombination has taken place in the tissue- and genotype-specific manner (Figure 3B). K14-cre–Driven Apc Loss Induced Aberrant Hair Follicles throughout the Epidermis To understand the basis for delayed and abnormal hair development in the KA mutants, we conducted a histological and immunohistochemical examination (Figure 4). The hair follicle is an epidermal appendage that consists of an upper permanent portion, and a lower cycling portion that produces the hair [22,23]. The outer root sheath (ORS) is contiguous with and biochemically similar to the basal layer of the epidermis. The inner layers of the hair follicle include three concentric layers of inner root sheath and three concentric layers of hair-producing cells. At the base of the hair follicle is the germinative hair follicle bulb, which contains rapidly proliferating “matrix” cells that differentiate to populate all of the layers of the inner root sheath and the hair shaft itself [22]. During the anagen phase of the hair cycle (until P15), hair follicles of phenotypically normal mice grew deeply into the subcutaneous fat and were uniformly spaced and aligned in parallel arrays at a specific angle relative to the skin surface (Figure 4A). In contrast, KA mutant follicles were irregularly spaced and often seen as disoriented and clamped invaginations at P3 that became even more remarkable at P12 when the mutant mice were covered by fur coat (Figure 4F). Bulbs were often bent in addition to being irregularly angled to one another and their sizes and locations were often variable. Clusters of multiple invaginations or dysplastic follicular structures were frequently observed throughout the epidermis, whereas other regions showed gaps with no follicles. Serial sectioning indicated that some of the hair follicles in the P12 mutant skin were not properly formed or shorter than normal. Taken together, these features could account for the apparently delayed, followed by outgrowth, of the short and shaggy-looking fur coat of these mutant mice. Figure 4 Histological and Immunochemical Examination of P12 Skin and Teeth (A–E) P12 normal skin. (F–J) P12 mutant skin. (K–N) P12 normal oral cavity. (O–R) P12 mutant oral cavity. Stained with H&E for histology (A, F, K–L, O–P), Ki67 (B, G), β-catenin (C, H, M, Q), K14 (D, I, N, R), and K6 (E, J). Aberrant follicular morphogenesis, characterized by formation of irregularly spaced, nonpolarized hair follicles, in mutant skin is evident. Despite the abnormal histology, proliferation seems to be confined to hair bulb-like structures (arrows in [G], inset [G′] at higher magnification), but in mutant skin (arrows in [H], inset [H′] at higher magnification) and oral cavity (arrows in insets [Q′] at higher magnification) elevated cytosolic localization of β-catenin is detected in some cells. Scale bars: 50 μm for (A–F), (H–J); 250 μm for (K) and (O); 100 μm for (G), (L–N), (P–R); 20 μm for (Q′). Apc is a regulator of β-catenin that is important for Wnt signaling. We examined the patterns of expression of β-catenin in the affected tissues. In the normal skin, β-catenin, a member of the adherens junction complex, was found in the ORS of hair follicles and basal layer of epidermis, where K14 expression is also observed (Figure 4C and 4D), whereas the expression of K1, involucrin, and loricrin (markers for spinous and granular layers of epidermis) was only observed in the nonbasal epidermis (unpublished data). The patterns of expression of K14, K1, involucrin, and loricrin, in skin from mutant and normal littermate mice at P3–P17, showed no significant differences in the terminal differentiation (Figure 4A–4D, 4F–4I). Similarly, the pattern of expression of K6, which is normally only expressed in the suprabasal or inner layer of the ORS of the hair follicle but not in the epidermis (Figure 4E), did not change. Due to the abnormal and disorganized structure of hair follicles themselves, K6 localization highlighted the histological abnormality (Figure 4J). Yet as in the normal skin, K6 was principally seen only in the suprabasal layer of the ORS that did not colocalize with the basal markers, K14 or K5 (Figure 4I and 4J). In normal skin, proliferating cells were detected in either the basal layer of epidermis or in germinative hair follicle bulbs at the base (Figure 4B). In the mutant skin, either BrdU incorporation or Ki67 expression was observed not only in cells in bulbs at the base of the hair follicle but also in bulb-like structures that were budding out from the ORS of the existing hair follicles (Figure 4G and 4G′). Each budding tip was becoming like a hair follicle bulb containing proliferating cells. Hence, despite the abnormal histology in the mutant skin, proliferation seems to be confined to bulb-like structures as in the normal skin (Figure 4G and 4G′). The exact locations of hair follicle bulbs were not as easy to define for some mutant follicles due to their disorganized structures. Interestingly, in the mutant skin, in addition to diffuse membrane-bound localization as in the normal skin, cells with strong cytosolic β-catenin localization were also observed frequently (Figure 4H and 4H′). These elevated β-catenin–expressing cells were usually surrounded by proliferating cells, forming bulb-like structures. Comparison of immunochemically stained serial sections showed that these intense cytosolic β-catenin stainings were usually found in either K14-positive K1-negative basal epidermis or K14-positive K6-negative basal ORS cells, and are surrounded by proliferating cells. To determine the initiation of hair follicle morphogenesis in these mutants, we examined the expression pattern of Sonic hedgehog (Shh), a factor expressed in hair bulbs in embryonic skin (Figure 5). The aberrant hair follicle morphogenesis is evident as early as E14.5 in mutant embryonic skin, by multiple apolarized expression of Shh throughout the epidermis (Figure 5B), whereas that of control embryos was well polarized and regularly spaced (Figure 5A). With development, control mouse hair follicles invaginate downward in a polarized manner (Figure 5C), whereas those of mutant embryos were completely irregular and apolarized (Figure 5D). It was also noted that the size of each “budding” follicle, as detected by Shh expression, was variable (Figure 5D). The intensity of Shh staining was generally stronger in mutant skin than in the normal skin. The aberrant initiation of multiple hair placodes during early hair follicle morphogenesis was also evident by the whole-mount in situ hybridization (ISH) of E15.5 mutant embryos for β-catenin (Figure 5F and 5F′). The expression pattern of β-catenin in embryos clearly demonstrated the formation of regular arrays of hair placodes in the normal embryonic skin (Figure 5E and 5E′), but such regular patterning was lost, and often tightly clustered abnormal hair placodes were initiated in mutant embryonic skin (Figure 5F′). Aberrant hair placodes were also evident throughout the skin surface of limbs in E15.5 mutants (Figure 5F), whereas those of the control embryos had not yet formed (Figure 5E). Most interestingly, in the mutant footpads, where hair placodes do not normally form (Figure 5G), we also found ectopic irregularly sized and spaced hair placodes, indicating that the footpads still have the potential to form hair placodes in the absence of the Apc gene (Figure 5H). Figure 5 Expression of Shh and β-catenin Transcripts in Normal (ApcCKO/CKO) and Mutant (K14-cre; ApcCKO/CKO) Embryonic Skin (A–D) Section ISH with Shh probe in E14.5 normal (A), E14.5 mutant (B), E16.5 normal (C), and E16.5 mutant (D) skin. Broken lines indicate the interface between epithelium and mesenchyme. Scale bars: 50 μm. Whole mount in situ detection of β-catenin in E15.5 normal (E, G), mutant (F, H) embryos. Aberrant initiation of multiple hair placodes is evident at E14.5. Loss of K14-driven Apc loss caused aberrant pattern formation (F′) and formed ectopic hair placodes in normally hairless foot pads (H, arrows) which are absent in normal (G). These results collectively suggest that the terminal differentiation does take place normally in the mutant skin, but initiation of embryonic hair follicle morphogenesis is severely disrupted, accompanied by a continuous ectopic hair follicle morphogenesis in postnatal mutant skin. Effects of K14-cre–Driven Loss of Apc in Other Epidermal Appendages Similar to the biology of hair follicles, K14-cre–driven loss of Apc also affected the development of other epidermal appendages that depend on epithelial–mesenchymal interactions for their formation. The most striking of these was dental dysplasia (Figure 4K–4R). Tooth development is normally initiated between E11 and E12 by invagination of ectodermally derived oral epithelium into the underlying cranial neural crest–derived mesenchyme, generating a tooth germ. Despite the grossly toothless phenotype of KA mutants, histological analysis of their oral cavities revealed the formation of multiple tooth buds at each location. These aberrant teeth obviously failed to grow out during the dietary transition from milk to solid food. Analogous to the expression patterns of K14 and β-catenin in the normal skin, diffuse membrane-bound expression of β-catenin was detected in K14-expressing oral epithelium and ameloblasts of normal mice. In mutants, some of the K14-expressing cells also showed strong cytosolic/nuclear β-catenin staining, as observed in the mutant skin (Figure 4Q, 4Q′, and 4R). Initiation of ectopic tooth buds in the mutant mice was evident at E15.5 by extra dots of Shh expression adjacent to the primary teeth (data not shown). Loss of Apc also leads to hyperplasia in squamous epithelia of cornea, oral, salivary, and Hardarian glands (unpublished data). Squamous metaplasia to hair follicle–like structures, ectopic hair follicle morphogenesis was also observed in these epithelia. K14-cre–Driven Apc Loss Results in Hypoplastic/Athymic Mice Thymus is an organ that is also known to have K14 expression [16]. It represents the primary lymphoid organ for thymocyte development and selection. Distinct population of TECs of cortex and medulla mediates both of these critical functions. Cortical and medullary TEC subsets are characterized by differential expression of four keratin species: K8, K18, K5, and K14. The normal thymus is a lobulated lymphoid organ, each lobule clearly showing the two distinct TEC compartments, an outer cortex and an inner medulla (Figure 6). There were no major differences in the histology of thymus between the ages P3 to P17 in phenotypically normal littermates. As shown in the H&E staining of thymus, the cortex was formed of dense lymphoid tissue that lacks nodules (Figure 6A). Since the stroma of the medulla is less heavily infiltrated with lymphocytes than the cortex, the medulla stained more lightly than the cortex. In normal mice, the thymus retains its size until the young adult age and regresses thereafter by atrophy. In the normal young mice we examined (P3–P17), it is evident that thymocytes were mitotically active in the cortex as determined by BrdU immunostaining (Figure 6B). Immunohistochemistry of normal thymus from P3 to P17 mice showed a similar staining pattern for K14 in that its expression was restricted to a small population of TECs in the inner medullary region and in the keratinocytes in Hassall's corpuscles (Figure 6D). Diffuse cytoplasmic staining for β-catenin was also detected in the medullary epithelial cells (Figure 6C). In contrast to K14 expression, diffuse staining for K8 was observed in epithelial cells both in the medulla and cortex (Figure S3). K1 staining was not detected in young mice at P3 but in older mice it was detected in differentiated keratinocytes in some of Hassall's corpuscles (Figure S3). Figure 6 Histological and Immunochemical Examination of Thymus (A–D) P3 normal thymus. (E–G) Mild P3 mutant thymus. (H–K) Severe P3 mutant thymus. (L–O) P13 mutant thymus. Stained with H&E for histology (A, E, H, L), BrdU (B, I, M), β-catenin (C, F, J, N), and K14 (D, G, K, O). (B) Actively dividing thymocytes are visible at the superficial edge of cortex of normal P3 thymus. Note the progression of histological abnormalities in the mutant thymus from mild P3, severe P3 to P13 (A, E, H, L). Scale bars, 20 μm. The histological abnormalities of thymus were evident as early as P3 in KA mutants (Figure 6E and 6H). The thymus was made of two lobules as in the normal mice but the mutant thymus was significantly smaller in size than that of the age-matched controls (Figure 2G). Interestingly, variations in the phenotypic severity of the mutant pups at P3 were prominently reflected in the extent of histological abnormalities of thymus. A P3 KA mutant pup that showed milder phenotype with a comparable body weight to its normal littermates (Figure 2A, M2) showed milder thymus abnormalities (Figure 6E) compared to its more severe mutant littermate (Figure 2A, M1; Figure 6H). The milder P3 mutant thymus was already much smaller in size compared to those of normal littermates (data not shown) but two epithelial compartments of thymus were histologically still distinguishable, with colonization of thymocytes evident in the cortex. However, there were small populations of lightly stained cells by H&E extending from the edge of the outer cortex towards inner medulla (Figure 6E), and these cells showed intense nuclear β-catenin staining whereas the rest of the medullary cells showed diffuse β-catenin staining pattern similar to that of the control (Figure 6F). Localization of K14 was limited to a few cells in the medulla and some overlapped with K8 localization (Figure 6G). In the other P3 mutant thymus the distinct thymic epithelial compartments have been lost completely, and only a few lymphocytes were remaining at the edges and some in the middle (Figure 6H). Proliferative activities were no longer observed in thymocytes as prominently as in the normal thymus, but the epithelial cells seemed to be forming concentric structures (Figure 6I). Unlike in the normal or mild mutant thymi, the severe P3 mutant thymus showed extensive K14 expression that overlapped with K8 expression (Figure 6K). These cells were more like basal cells of the skin than TECs and were adjacent to the most immature looking cells that were showing strong nuclear and cytoplasmic β-catenin staining (Figure 6J). The nuclear staining of β-catenin was not observed in the normal age-matched thymus (Figure 6C). Most notably, the K14 and β-catenin staining patterns were mutually exclusive (Figure 6J and 6K). At P10–P13, the mutant thymus consisted of numerous enlarged Hassall's corpuscle–like structures, made of arrays of K14- and K8-expressing keratinizing epithelial cells surrounding large keratin deposits (Figure 6L and 6O). There were numerous neutrophils and macrophages infiltrating the thymus in response to these keratins; hence, these structures could be called pyogranuloma. Varying degrees of differentiation-specific markers depending on the age of mice, in this case K1 and involucrin that are normally present only in Hassall's corpuscles, were also detected in mutant thymi (Figure S3). In these mice no thymocytes were detectable. BrdU incorporation was only observed in very few keratinizing epithelial cells, looking somewhat similar to the pattern of mature skin (Figure 6M). The diffuse expression of β-catenin was also present in these epithelial cells, and at this age fewer cells were positive for nuclear β-catenin staining (Figure 6N). As in the younger mutant mice, however, nuclear localization of β-catenin was only observed in K14-negative cells that looked like undifferentiated basal cells. In older P17 mice, the histopathology and keratin expression pattern of the mutant thymus was similar to that of P13 except for the fact that β-catenin expression became increasingly diffuse and appeared to colocalize with K8/K14 expression (data not shown). This coincided with fewer immature cells in the older mutant thymus. Collectively, these results suggest that loss of Apc and consequent stabilization of β-catenin in K14-expressing TECs lead to their aberrant proliferation and differentiation to keratinocytes, causing massive squamous metaplasia, rather than to form either medullary or cortical TECs. Loss of proper TEC compartments consequently resulted in loss of thymocytes for maturation and the mice to be “athymic.” Discussion Apc
T19005 37388-37409 GO:0016055 denotes Wnt signaling pathway
T19006 37466-37471 NCBITaxon:9606 denotes Human
T19007 37481-37490 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T19008 37494-37497 PR_EXT:000004122 denotes APC
T19009 37565-37575 UBERON:0012652 denotes colorectal
T19010 37625-37635 UBERON:0012652 denotes colorectal
T19011 37678-37682 UBERON:0000104 denotes life
T19012 37787-37797 UBERON:0012652 denotes colorectal
T19013 37812-37823 NCBITaxon:1 denotes individuals
T19014 37841-37848 UBERON:0001155 denotes colonic
T19015 37875-37903 UBERON:0004908 denotes upper gastrointestinal tract
T19016 37942-37968 UBERON:0001782 denotes retinal pigment epithelium
T19017 37950-37957 CHEBI_EXT:26130 denotes pigment
T19018 38003-38012 UBERON:0002397 denotes maxillary
T19019 38017-38025 UBERON:0004288 denotes skeletal
T19020 38026-38031 UBERON:0001474 denotes bones
T19021 38037-38043 UBERON:0001091 denotes dental
T19022 38095-38099 NCBITaxon:10088 denotes mice
T19023 38104-38107 PR_EXT:000004122 denotes Apc
T19024 38152-38167 UBERON:0002108 denotes small intestine
T19025 38184-38191 UBERON:0000922 denotes embryos
T19026 38192-38195 GO:0016265 denotes die
T19027 38203-38215 GO:0007369 denotes gastrulation
T19028 38259-38262 PR_EXT:000004122 denotes Apc
T19029 38271-38278 UBERON:0000479 denotes tissues
T19030 38290-38312 UBERON:0001555 denotes gastrointestinal tract
T19031 38320-38324 UBERON:0000104 denotes life
T19032 38328-38335 NCBITaxon:33208 denotes animals
T19033 38358-38367 UBERON:0000922 denotes embryonic
T19034 38368-38377 GO_EXT:fatality_or_lethality denotes lethality
T19035 38394-38397 PR_EXT:000004122 denotes Apc
T19036 38426-38431 NCBITaxon:10088 denotes mouse
T19037 38462-38468 SO_EXT:0001023 denotes allele
T19038 38472-38475 PR_EXT:000004122 denotes Apc
T19039 38477-38480 PR_EXT:000004122 denotes Apc
T19040 38494-38498 SO_EXT:0000147 denotes exon
T19041 38509-38512 PR_EXT:000004122 denotes Apc
T19042 38516-38523 SO:0000357 denotes flanked
T19043 38527-38541 SO_EXT:0000346 denotes loxP sequences
T19044 38558-38562 NCBITaxon:10088 denotes mice
T19045 38583-38589 SO_EXT:0001023 denotes allele
T19046 38637-38641 NCBITaxon:10088 denotes mice
T19047 38677-38680 PR_EXT:000004122 denotes Apc
T19048 38686-38692 UBERON:0000479 denotes tissue
T19049 38785-38788 PR_EXT:000004122 denotes Apc
T19050 38789-38793 SO_EXT:0000704 denotes gene
T19051 38797-38802 CL_GO_EXT:cell denotes cells
T19052 38808-38815 GO:0010467 denotes express
T19053 38816-38819 PR_EXT:000009454 denotes K14
T19054 38832-38836 NCBITaxon:10088 denotes mice
T19055 38865-38868 PR_EXT:000004122 denotes Apc
T19056 38872-38878 SO_EXT:0001023 denotes allele
T19057 38893-38896 PR_EXT:000009454 denotes K14
T19058 38901-38910 SO_EXT:0000902 denotes transgene
T19059 38918-38922 NCBITaxon:10088 denotes mice
T19060 38944-38948 GO:0016265 denotes died
T19061 38985-38989 UBERON:0001037 denotes hair
T19062 38991-38996 UBERON:0001091 denotes tooth
T19063 39002-39008 UBERON:0002370 denotes thymus
T21897 39022-39025 PR_EXT:000004122 denotes Apc
T21898 39030-39043 UBERON:0002073 denotes Hair Follicle
T21899 39030-39057 GO:0031069 denotes Hair Follicle Morphogenesis
T21900 39076-39089 UBERON:0002073 denotes hair follicle
T21901 39076-39101 GO:0001942 denotes hair follicle development
T21902 39155-39163 UBERON_EXT:placode denotes placodes
T21903 39179-39189 UBERON:0000483 denotes epithelium
T21904 39193-39201 GO_EXT:reaction_or_response denotes response
T21905 39215-39221 UBERON_EXT:skin_or_dermis denotes dermal
T21906 39278-39287 CHEBI:36357 denotes molecules
T21907 39312-39319 UBERON_EXT:placode denotes placode
T21908 39385-39406 GO:0016055 denotes Wnt signaling pathway
T21909 39414-39420 UBERON:0002067 denotes dermis
T21910 39463-39469 UBERON_EXT:skin_or_dermis denotes dermal
T21911 39505-39515 UBERON:0000483 denotes epithelial
T21912 39516-39525 PR_EXT:000002198 denotes β-catenin
T21913 39526-39535 GO_EXT:cell_communication_or_signaling_or_signal_transduction denotes signaling
T21914 39540-39550 GO:0010467 denotes expression
T21915 39554-39564 CHEBI_SO_EXT:N_terminus_or_N_terminal_region denotes N-terminal
T21916 39565-39574 SO_EXT:sequence_truncation_process denotes truncated
T21917 39611-39620 PR_EXT:000002198 denotes β-catenin
T21918 39632-39642 GO:0010467 denotes expression
T21919 39646-39650 PR_EXT:000009751 denotes Lef1
T21920 39668-39677 UBERON_EXT:follicle denotes follicles
T21921 39686-39691 NCBITaxon:10088 denotes mouse
T21922 39696-39701 NCBITaxon_UBERON_EXT:chick denotes chick
T21923 39702-39706 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T21924 39728-39743 GO_EXT:negative_regulation denotes down-regulation
T21925 39747-39756 PR_EXT:000002198 denotes β-catenin
T21926 39757-39766 GO_EXT:cell_communication_or_signaling_or_signal_transduction denotes signaling
T21927 39776-39780 PR_EXT:000009751 denotes Lef1
T21928 39800-39810 GO:0010467 denotes expression
T21929 39818-39827 CHEBI_EXT:35222 denotes inhibitor
T21930 39828-39832 PR_EXT:000006499 denotes Dkk1
T21931 39848-39856 SO_EXT:sequence_deletion_entity_or_process denotes deletion
T21932 39860-39869 PR_EXT:000002198 denotes β-catenin
T21933 39873-39882 UBERON:0007376 denotes epidermis
T21934 39903-39912 UBERON:0010419 denotes vibrissae
T21935 39922-39928 UBERON:0010509 denotes pelage
T21936 39929-39938 UBERON_EXT:follicle denotes follicles
T21937 39942-39946 NCBITaxon:10088 denotes mice
T21938 39973-39976 PR_EXT:000009454 denotes K14
T21939 39984-39987 PR_EXT:000004122 denotes Apc
T21940 39996-40014 UBERON:0000924 denotes embryonic ectoderm
T21941 40083-40095 UBERON:0005086 denotes hair placode
T21942 40111-40119 UBERON_EXT:follicle denotes follicle
T21943 40120-40133 GO:0009653 denotes morphogenesis
T21944 40205-40215 UBERON:0008281 denotes tooth buds
T21945 40286-40296 UBERON:0000483 denotes epithelial
T21946 40297-40306 PR_EXT:000002198 denotes β-catenin
T21947 40307-40316 GO_EXT:cell_communication_or_signaling_or_signal_transduction denotes signaling
T21948 40324-40331 UBERON_EXT:placode denotes placode
T21949 40366-40369 PR_EXT:000004122 denotes Apc
T21950 40373-40389 _FRAGMENT denotes specification of
T21951 40411-40421 GO:0048866 denotes stem cells
T21952 40400-40410 _FRAGMENT denotes ectodermal
T21953 40416-40421 GO:0001715 denotes cells
T21954 40390-40410 UBERON:0000924 denotes embryonic ectodermal
T21955 40390-40399 _FRAGMENT denotes embryonic
T21956 40411-40421 CL:0002322 denotes stem cells
T21957 40416-40421 CL:0000221 denotes cells
T21958 40416-40421 CL_GO_EXT:cell denotes cells
T21959 40435-40448 UBERON:0002073 denotes hair follicle
T21960 40468-40471 PR_EXT:000004122 denotes Apc
T21961 40475-40490 GO_EXT:negative_regulation denotes down-regulation
T21962 40494-40503 PR_EXT:000002198 denotes β-catenin
T21963 40513-40516 PR_EXT:000004122 denotes Apc
T21964 40550-40560 GO:0010467 denotes expression
T21965 40564-40573 PR_EXT:000002198 denotes β-catenin
T21966 40577-40587 UBERON:0000924 denotes ectodermal
T21967 40577-40593 CL:0000221 denotes ectodermal cells
T21968 40588-40593 CL_GO_EXT:cell denotes cells
T21969 40605-40617 UBERON:0005086 denotes hair placode
T21970 40605-40627 GO:0060789 denotes hair placode formation
T21971 40653-40663 UBERON_EXT:follicle denotes follicular
T21972 40664-40670 GO_EXT:biological_growth_entity_or_process denotes growth
T21973 40686-40695 UBERON:0000922 denotes embryonic
T21974 40696-40705 UBERON:0007376 denotes epidermis
T21975 40721-40729 UBERON:0013623 denotes footpads
T21976 40746-40750 UBERON:0001037 denotes hair
T21977 40859-40865 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T21978 40866-40870 NCBITaxon:10088 denotes mice
T21979 40900-40903 PR_EXT:000009454 denotes K14
T21980 40913-40923 SO_EXT:transgenic_entity denotes transgenic
T21981 40924-40928 NCBITaxon:10088 denotes mice
T21982 40929-40939 GO:0010467 denotes expressing
T21983 40947-40956 PR_EXT:000002198 denotes β-catenin
T21984 40967-40974 GO:0065007 denotes control
T21985 40978-40981 PR_EXT:000009454 denotes K14
T21986 40982-40990 SO_EXT:0000167 denotes promoter
T21987 41000-41003 PR_EXT:000009454 denotes K14
T21988 41004-41008 PR_EXT:000009751 denotes Lef1
T21989 41009-41019 SO_EXT:transgenic_entity denotes transgenic
T21990 41020-41024 NCBITaxon:10088 denotes mice
T21991 41049-41055 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T21992 41056-41060 NCBITaxon:10088 denotes mice
T21993 41095-41098 PR_EXT:000009454 denotes K14
T21994 41099-41103 PR_EXT:000009751 denotes Lef1
T21995 41104-41108 NCBITaxon:10088 denotes mice
T21996 41118-41121 PR_EXT:000009454 denotes K14
T21997 41131-41141 SO_EXT:transgenic_entity denotes transgenic
T21998 41142-41146 NCBITaxon:10088 denotes mice
T21999 41168-41174 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22000 41175-41179 NCBITaxon:10088 denotes mice
T22001 41240-41243 PR_EXT:000009454 denotes K14
T22002 41259-41262 PR_EXT:000009454 denotes K14
T22003 41272-41282 SO_EXT:transgenic_entity denotes transgenic
T22004 41283-41287 NCBITaxon:10088 denotes mice
T22005 41305-41311 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22006 41312-41316 NCBITaxon:10088 denotes mice
T22007 41342-41351 UBERON:0010166 denotes hair coat
T22008 41384-41392 PATO_UBERON_EXT:neonate_or_newborn denotes neonatal
T22009 41393-41398 UBERON:0001037 denotes hairs
T22010 41428-41431 PR_EXT:000009454 denotes K14
T22011 41432-41436 PR_EXT:000009751 denotes Lef1
T22012 41437-41441 NCBITaxon:10088 denotes mice
T22013 41454-41457 PR_EXT:000009454 denotes K14
T22014 41467-41471 NCBITaxon:10088 denotes mice
T22015 41473-41482 UBERON:0000922 denotes embryonic
T22016 41473-41482 _FRAGMENT denotes embryonic
T22017 41497-41510 GO:0048598 denotes morphogenesis
T22018 41483-41496 UBERON:0002073 denotes hair follicle
T22019 41483-41510 GO:0031069 denotes hair follicle morphogenesis
T22020 41536-41540 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T22021 41566-41573 GO:0007567 denotes natally
T22022 41697-41700 PR_EXT:000009454 denotes K14
T22023 41701-41709 SO_EXT:0000167 denotes promoter
T22024 41742-41752 GO:0010467 denotes expression
T22025 41844-41854 GO:0010467 denotes expression
T22026 41858-41866 SO_EXT:0000167 denotes promoter
T22027 41867-41876 SO_EXT:0000902 denotes transgene
T22028 41877-41886 SO_EXT:engineered_biological_sequence denotes construct
T22029 41890-41900 SO_EXT:transgenic_entity denotes transgenic
T22030 41901-41905 NCBITaxon:10088 denotes mice
T22031 41967-41983 SO_EXT:0000366 denotes integration site
T22032 41991-42000 SO_EXT:0000902 denotes transgene
T22033 42008-42013 NCBITaxon:10088 denotes mouse
T22034 42014-42020 SO_EXT:0001026 denotes genome
T22035 42039-42062 SO_EXT:0000366 denotes location of integration
T22036 42068-42083 GO_EXT:transcription denotes transcriptional
T22037 42110-42119 SO_EXT:0000902 denotes transgene
T22038 42207-42220 GO:0009790 denotes embryogenesis
T22039 42257-42267 GO:0010467 denotes expression
T22040 42275-42278 PR_EXT:000009454 denotes K14
T22041 42288-42297 SO_EXT:0000902 denotes transgene
T22042 42324-42332 SO_EXT:0000167 denotes promoter
T22043 42360-42373 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T22044 42391-42395 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T22045 42399-42402 PR_EXT:000009454 denotes K14
T22046 42407-42417 SO_EXT:transgenic_entity denotes transgenic
T22047 42418-42422 NCBITaxon:10088 denotes mice
T22048 42451-42454 PR_EXT:000009454 denotes K14
T22049 42468-42478 SO_EXT:sequence_truncation_entity_or_process denotes truncation
T22050 42486-42489 PR_EXT:000004122 denotes Apc
T22051 42490-42494 SO_EXT:0000704 denotes gene
T22052 42562-42575 UBERON:0002073 denotes hair follicle
T22053 42562-42588 GO:0031069 denotes hair follicle morphgenesis
T22054 42647-42657 SO_EXT:transgenic_entity denotes transgenic
T22055 42672-42682 GO:0010467 denotes expression
T22056 42686-42695 SO_EXT:0000902 denotes transgene
T22057 42715-42729 _FRAGMENT denotes basal cells of
T22058 42734-42743 CL:0002187 denotes epidermis
T22059 42721-42726 CL_GO_EXT:cell denotes cells
T22060 42721-42729 _FRAGMENT denotes cells of
T22061 42752-42773 CL:0002561 denotes ORS of hair follicles
T22062 42734-42743 UBERON:0007376 denotes epidermis
T22063 42752-42773 UBERON:0005942 denotes ORS of hair follicles
T22064 42785-42788 PR_EXT:000009454 denotes K14
T22065 42789-42797 SO_EXT:0000167 denotes promoter
T22066 42813-42823 GO:0010467 denotes expression
T22067 42827-42836 SO_EXT:0000902 denotes transgene
T22068 42871-42874 PR_EXT:000009454 denotes K14
T22069 42875-42885 GO:0010467 denotes expressing
T22070 42886-42891 CL_GO_EXT:cell denotes cells
T22071 42903-42916 GO_RO_EXT:developmental_differentiation_process denotes differentiate
T22072 42945-42948 PR_EXT:000009454 denotes K14
T22073 42962-42970 SO_EXT:sequence_deletion_entity_or_process denotes deletion
T22074 42974-42977 PR_EXT:000004122 denotes Apc
T22075 42994-42997 PR_EXT:000004122 denotes Apc
T22076 42998-43006 SO_EXT:sequence_alteration_entity_or_process denotes mutation
T22077 43019-43022 PR_EXT:000009454 denotes K14
T22078 43023-43031 SO_EXT:0000167 denotes promoter
T22079 43039-43044 CL_GO_EXT:cell denotes cells
T22080 43067-43071 CL_GO_EXT:cell denotes cell
T22081 43067-43078 UBERON:0000119 denotes cell layers
T22082 43101-43104 PR_EXT:000009454 denotes K14
T22083 43105-43113 SO_EXT:0000167 denotes promoter
T22084 43164-43184 UBERON:0010402 denotes suprabasal epidermis
T22085 43200-43210 UBERON:0000483 denotes epithelium
T22086 43218-43231 UBERON:0002073 denotes hair follicle
T22087 43250-43259 PR_EXT:000002198 denotes β-catenin
T22088 43273-43292 UBERON_EXT:cell_clump_or_cluster_or_group_or_mass_or_population denotes population of cells
T22089 43287-43292 CL_GO_EXT:cell denotes cells
T22090 43387-43396 PR_EXT:000002198 denotes β-catenin
T22091 43397-43407 GO:0010467 denotes expression
T22092 43418-43420 PR_EXT:000009450 denotes K1
T22093 43425-43427 PR_EXT:keratin_6 denotes K6
T22094 43437-43451 GO_PATO_RO_EXT:developmental_differentiation_process_or_quality denotes differentiated
T22095 43452-43457 CL_GO_EXT:cell denotes cells
T22096 43465-43470 GO:0007567 denotes natal
T22097 43471-43477 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22098 43478-43482 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T22099 43527-43530 PR_EXT:000004122 denotes Apc
T22100 43562-43571 PR_EXT:000002198 denotes β-catenin
T22101 43590-43593 PR_EXT:000009454 denotes K14
T22102 43594-43604 GO:0010467 denotes expressing
T22103 43627-43636 PR_EXT:000002198 denotes β-catenin
T22104 43637-43647 GO:0010467 denotes expression
T22105 43664-43668 CL_GO_EXT:cell denotes cell
T22106 43664-43687 GO:0001709 denotes cell fate determination
T22107 43711-43722 CL:0000646 denotes basal cells
T22108 43717-43722 CL_GO_EXT:cell denotes cells
T22109 43807-43810 PR_EXT:000004122 denotes Apc
T22110 43851-43866 GO_EXT:negative_regulation denotes down-regulation
T22111 43870-43879 PR_EXT:000002198 denotes β-catenin
T22112 43966-43972 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22113 43973-43977 NCBITaxon:10088 denotes mice
T22114 44000-44010 SO_EXT:transgenic_entity denotes transgenic
T22115 44011-44015 NCBITaxon:10088 denotes mice
T22116 44089-44102 UBERON:0002073 denotes hair follicle
T22117 44089-44116 GO:0031069 denotes hair follicle morphogenesis
T22118 44118-44121 PR_EXT:000009454 denotes K14
T22119 44137-44140 PR_EXT:000004122 denotes Apc
T22120 44170-44180 UBERON:0008281 denotes tooth buds
T22121 44192-44206 UBERON:0002073 denotes hair follicles
T22122 44273-44283 UBERON:0000483 denotes epithelium
T22123 44288-44298 UBERON:0003104 denotes mesenchyme
T22124 44344-44354 UBERON:0008281 denotes tooth buds
T22125 44364-44371 NCBITaxon:33208 denotes animals
T22126 44375-44385 GO:0010467 denotes expressing
T22127 44386-44390 PR_EXT:000009751 denotes Lef1
T22128 44437-44442 GO:0007567 denotes birth
T22129 44469-44472 PR_EXT:000004122 denotes Apc
T22130 44503-44512 UBERON:0000922 denotes embryonic
T22131 44503-44512 _FRAGMENT denotes embryonic
T22132 44519-44530 GO:0009790 denotes development
T22133 44513-44518 UBERON:0001091 denotes tooth
T22134 44562-44565 PR_EXT:000014841 denotes Shh
T22135 44566-44576 GO:0010467 denotes expression
T22136 44586-44595 UBERON:0000922 denotes embryonic
T22137 44596-44611 UBERON:0002424 denotes oral epithelium
T22138 44674-44684 UBERON:0008281 denotes tooth buds
T22139 44739-44744 UBERON:0001091 denotes teeth
T22140 44772-44778 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22141 44779-44783 NCBITaxon:10088 denotes mice
T22142 44793-44798 UBERON:0001091 denotes tooth
T22143 44824-44829 UBERON:0001091 denotes tooth
T22144 44856-44862 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22145 44863-44867 NCBITaxon:10088 denotes mice
T22146 44901-44911 SO_EXT:transgenic_entity denotes transgenic
T22147 44912-44916 NCBITaxon:10088 denotes mice
T22148 44925-44932 GO:0007567 denotes natally
T22149 44933-44939 GO_EXT:fatality_or_lethality denotes lethal
T22150 44953-44959 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22151 44960-44964 NCBITaxon:10088 denotes mice
T22152 45042-45048 UBERON:0000062 denotes organs
T22153 45055-45059 NCBITaxon:10088 denotes mice
T22154 45089-45098 GO_EXT:fatality_or_lethality denotes lethality
T22155 45131-45138 SO_EXT:sequence_altered_entity denotes mutants
T22156 45202-45206 CHEBI_EXT:33290 denotes food
T22157 45216-45223 UBERON:0000945 denotes stomach
T22158 45243-45250 SO_EXT:sequence_altered_entity denotes mutants
T22159 45262-45266 GO:0016265 denotes died
T22160 45282-45288 UBERON_EXT:skin_or_dermis denotes Dermal
T22161 45289-45292 CHEBI_UBERON_EXT:triglyceride_or_adipose_tissue denotes fat
T22162 45312-45318 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T22163 45319-45323 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T22164 45394-45399 UBERON:0001091 denotes teeth
T22165 45429-45436 SO_EXT:sequence_altered_entity denotes mutants
T22166 45463-45467 NCBITaxon_UBERON_EXT:pup denotes pups
T22167 45479-45485 GO:0001967 denotes nursed
T22168 45530-45535 UBERON:0001091 denotes teeth
T22169 45564-45569 GO:0016265 denotes death
T22170 45625-45630 UBERON:0001091 denotes teeth
T22171 45635-45649 UBERON:0001911 denotes mammary glands
T22172 45672-45676 NCBITaxon:10088 denotes mice
T22173 45690-45694 PR_EXT:000009751 denotes Lef1
T22174 45711-45721 GO:0010467 denotes expressing
T22175 45722-45726 PR_EXT:000006499 denotes Dkk1
T22176 45845-45854 UBERON:0008281 denotes tooth bud
T22177 45894-45899 UBERON:0001091 denotes teeth
T22178 45904-45908 NCBITaxon:10088 denotes mice
T22179 45943-45947 UBERON:0000104 denotes life
T22180 46007-46016 PR_EXT:000002198 denotes β-catenin
T22181 46034-46038 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T22182 46043-46048 UBERON:0001091 denotes tooth
T25221 46076-46079 PR_EXT:000004122 denotes Apc
T25222 46084-46090 UBERON:0002370 denotes Thymus
T25223 46084-46104 GO:0048538 denotes Thymus Organogenesis
T25224 46137-46140 PR_EXT:000009454 denotes K14
T25225 46156-46159 PR_EXT:000004122 denotes Apc
T25226 46180-46186 UBERON:0002370 denotes thymus
T25227 46311-46320 CL:0000893 denotes thymocyte
T25228 46321-46331 GO_PATO_EXT:biological_maturation denotes maturation
T25229 46347-46351 NCBITaxon:10088 denotes mice
T25230 46353-46359 UBERON:0002370 denotes thymic
T25231 46404-46409 UBERON:0007023 denotes adult
T25232 46410-46416 UBERON:0002370 denotes thymus
T25233 46417-46420 PR_EXT:000009454 denotes K14
T25234 46421-46431 GO:0010467 denotes expression
T25235 46455-46457 PR_EXT:000009481 denotes K5
T25236 46474-46483 UBERON:0000958 denotes medullary
T25238 46518-46520 PR_EXT:000009481 denotes K5
T25239 46522-46526 CL:0002293 denotes TECs
T25240 46534-46540 UBERON:0001851 denotes cortex
T25241 46551-46558 UBERON:0001851 denotes cortico
T25242 46559-46568 UBERON:0000958 denotes medullary
T25243 46622-46625 PR_EXT:000009454 denotes K14
T25244 46627-46631 CL:0002293 denotes TECs
T25245 46641-46648 GO:0010467 denotes express
T25246 46649-46651 PR_EXT:000009495 denotes K8
T25247 46683-46692 UBERON:0000958 denotes medullary
T25248 46711-46713 PR_EXT:000009495 denotes K8
T25249 46714-46717 PR_EXT:000009454 denotes K14
T25250 46741-46743 PR_EXT:000009495 denotes K8
T25251 46744-46747 PR_EXT:000009454 denotes K14
T25252 46824-46830 UBERON:0002370 denotes thymus
T25253 46831-46834 PR_EXT:000009454 denotes K14
T25254 46835-46845 GO:0010467 denotes expression
T25255 46873-46882 UBERON:0000958 denotes medullary
T25256 46873-46887 CL:0002365 denotes medullary TECs
T25257 46909-46911 PR_EXT:000009495 denotes K8
T25258 46912-46922 GO:0010467 denotes expression
T25259 46948-46952 CL:0002293 denotes TECs
T25260 47028-47037 GO:0010467 denotes expressed
T25261 47050-47054 CL:0002293 denotes TECs
T25262 47120-47127 SO_EXT:sequence_altered_entity denotes mutants
T25263 47206-47212 UBERON:0002370 denotes thymus
T25264 47247-47254 SO_EXT:sequence_altered_entity denotes mutants
T25265 47299-47305 UBERON:0002370 denotes thymus
T25266 47311-47317 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T25267 47318-47323 UBERON:0002370 denotes thymi
T25268 47387-47390 PR_EXT:000009454 denotes K14
T25269 47433-47439 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T25270 47440-47446 UBERON:0002370 denotes thymus
T25271 47459-47478 UBERON_EXT:cell_clump_or_cluster_or_group_or_mass_or_population denotes population of cells
T25272 47473-47478 CL_GO_EXT:cell denotes cells
T25273 47496-47503 GO:0005634 denotes nuclear
T25274 47504-47513 PR_EXT:000002198 denotes β-catenin
T25275 47538-47543 CL_GO_EXT:cell denotes cells
T25276 47544-47554 GO:0010467 denotes expressing
T25277 47555-47558 PR_EXT:000009454 denotes K14
T25278 47574-47591 UBERON:0003846 denotes thymic epithelial
T25279 47632-47638 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T25280 47639-47645 UBERON:0002370 denotes thymus
T25281 47688-47703 GO_RO_EXT:developmental_differentiation_process denotes differentiation
T25282 47707-47716 UBERON:0000958 denotes medullary
T25283 47707-47716 _FRAGMENT denotes medullary
T25284 47730-47734 CL:0002365 denotes TECs
T25285 47721-47729 UBERON:0001851 denotes cortical
T25286 47721-47734 CL:0002364 denotes cortical TECs
T25287 47739-47748 CL:0000893 denotes thymocyte
T25288 47817-47820 PR_EXT:000009454 denotes K14
T25289 47828-47831 PR_EXT:000004122 denotes Apc
T25290 47847-47852 CL_GO_EXT:cell denotes cells
T25291 47858-47865 GO:0005634 denotes nuclear
T25292 47866-47875 PR_EXT:000002198 denotes β-catenin
T25293 47880-47882 PR_EXT:000009495 denotes K8
T25294 47883-47886 PR_EXT:000009454 denotes K14
T25295 47904-47914 UBERON:0000483 denotes epithelial
T25296 47904-47920 CL:0000066 denotes epithelial cells
T25297 47915-47920 CL_GO_EXT:cell denotes cells
T25298 47968-47981 GO:0008283 denotes proliferation
T25299 47996-48010 UBERON_EXT:cell_clump_or_cluster_or_group_or_mass_or_population denotes group of cells
T25300 48005-48010 CL_GO_EXT:cell denotes cells
T25301 48023-48026 CL:0002293 denotes TEC
T25302 48051-48060 PR_EXT:000002198 denotes β-catenin
T25303 48061-48071 GO:0010467 denotes expression
T25304 48110-48120 UBERON:0000483 denotes epithelial
T25305 48110-48126 CL:0000066 denotes epithelial cells
T25306 48121-48126 CL_GO_EXT:cell denotes cells
T25307 48134-48141 GO:0005634 denotes nuclear
T25308 48142-48154 GO_PATO_EXT:biological_localization_process_or_quality denotes localization
T25309 48159-48161 PR_EXT:000009495 denotes K8
T25310 48162-48165 PR_EXT:000009454 denotes K14
T25311 48167-48172 CL_GO_EXT:cell denotes cells
T25312 48216-48226 UBERON:0000483 denotes epithelial
T25313 48216-48232 CL:0000066 denotes epithelial cells
T25314 48227-48232 CL_GO_EXT:cell denotes cells
T25315 48303-48314 CL:0000775 denotes neutrophils
T25316 48319-48330 CL:0000235 denotes macrophages
T25317 48343-48353 UBERON:0000483 denotes epithelial
T25318 48343-48359 CL:0000066 denotes epithelial cells
T25319 48354-48359 CL_GO_EXT:cell denotes cells
T25320 48389-48399 CL:0000893 denotes thymocytes
T25321 48463-48471 SO_EXT:sequence_deletion_entity_or_process denotes deletion
T25322 48475-48478 PR_EXT:000004122 denotes Apc
T25323 48482-48486 CL:0002293 denotes TECs
T25324 48508-48515 GO:0005634 denotes nuclear
T25325 48516-48528 GO_PATO_EXT:biological_localization_process_or_quality denotes localization
T25326 48532-48541 PR_EXT:000002198 denotes β-catenin
T25327 48576-48581 CL_GO_EXT:cell denotes cells
T25328 48582-48596 GO_PATO_RO_EXT:developmental_differentiation_process_or_quality denotes differentiated
T25329 48602-48615 CL:0000312 denotes keratinocytes
T25330 48621-48630 GO:0010467 denotes expressed
T25331 48636-48639 PR_EXT:000009454 denotes K14
T25332 48644-48646 PR_EXT:000009495 denotes K8
T25333 48663-48674 CL:0000646 denotes basal cells
T25334 48669-48674 CL_GO_EXT:cell denotes cells
T25335 48682-48686 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T25336 48699-48702 CL:0002293 denotes TEC
T25337 48730-48745 GO_RO_EXT:developmental_differentiation_process denotes differentiation
T25338 48755-48768 CL:0000312 denotes keratinocytes
T25339 48792-48809 UBERON:0003846 denotes thymic epithelial
T25340 48916-48927 CL:0000775 denotes neutrophils
T25341 48932-48943 CL:0000235 denotes macrophages
T25342 48962-48968 UBERON:0002370 denotes thymus
T25343 48985-48995 UBERON:0000483 denotes epithelial
T25344 49050-49056 UBERON:0002370 denotes thymus
T25345 49086-49096 CL:0000893 denotes thymocytes
T25346 49098-49101 PR_EXT:000009454 denotes K14
T25347 49117-49120 PR_EXT:000004122 denotes Apc
T25348 49149-49159 GO:0010467 denotes expression
T25349 49163-49172 PR_EXT:000002198 denotes β-catenin
T25350 49176-49180 CL:0002293 denotes TECs
T25351 49199-49207 GO_EXT:biological_direction_or_guidance denotes directed
T25352 49222-49232 UBERON:0000483 denotes epithelial
T25353 49222-49237 CL:0000066 denotes epithelial cell
T25354 49233-49237 CL_GO_EXT:cell denotes cell
T25355 49264-49279 GO_RO_EXT:developmental_differentiation_process denotes differentiation
T25356 49290-49298 UBERON:0001851 denotes cortical
T25357 49290-49298 _FRAGMENT denotes cortical
T25358 49312-49316 CL:0002364 denotes TECs
T25359 49302-49311 UBERON:0000958 denotes medullary
T25360 49302-49316 CL:0002365 denotes medullary TECs
T25361 49348-49357 CL:0000893 denotes thymocyte
T25362 49422-49432 CL:0000893 denotes thymocytes
T25363 49440-49446 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T25364 49447-49453 UBERON:0002370 denotes thymus
T25365 49491-49501 GO:0010467 denotes expression
T25366 49539-49543 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T25367 49554-49557 CL:0002293 denotes TEC
T25368 49582-49585 PR_EXT:000004122 denotes Apc
T25369 49598-49604 UBERON:0002370 denotes thymic
T25370 49598-49616 GO:0048538 denotes thymic development
T25371 49642-49651 CL:0000893 denotes thymocyte
T25372 49669-49672 PR_EXT:000004122 denotes Apc
T25373 49707-49710 PR_EXT:000004122 denotes Apc
T25374 49723-49727 NCBITaxon:10088 denotes mice
T25375 49739-49749 SO_EXT:transgenic_entity denotes transgenic
T25376 49750-49754 NCBITaxon:10088 denotes mice
T25377 49770-49773 PR_EXT:000009454 denotes K14
T25378 49781-49784 CL:0002293 denotes TEC
T25379 49802-49805 PR_EXT:000004122 denotes Apc
T25380 49846-49852 UBERON:0002370 denotes thymus
T25381 49846-49864 GO:0048538 denotes thymus development
T25382 49877-49887 CL:0000893 denotes thymocytes
T25383 49900-49904 CL:0002293 denotes TECs
T25384 49929-49935 UBERON:0001091 denotes dental
T25385 49986-49991 UBERON:0001091 denotes teeth
T25386 50025-50031 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T25387 50032-50036 NCBITaxon:10088 denotes mice
T25388 50107-50110 PR_EXT:000004122 denotes APC
T25389 50120-50128 SO_EXT:sequence_alteration_entity_or_process denotes mutation
T25390 50152-50158 UBERON:0001091 denotes odonto
T25391 50159-50173 UBERON:0000165 denotes stomatological
T25392 50389-50394 NCBITaxon:10088 denotes mouse
T25393 50440-50443 PR_EXT:000004122 denotes Apc
T25394 50465-50478 UBERON:0000467 denotes organ systems
T25395 50540-50545 NCBITaxon:9606 denotes human
T25396 50598-50601 PR_EXT:000004122 denotes Apc
T25397 50605-50608 PR_EXT:000009454 denotes K14
T25398 50609-50619 GO:0010467 denotes expressing
T25399 50620-50629 UBERON:0000922 denotes embryonic
T25400 50620-50635 CL:0002321 denotes embryonic cells
T25401 50630-50635 CL_GO_EXT:cell denotes cells
T25402 50652-50665 GO:0009653 denotes morphogenesis
T25403 50677-50681 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T25404 50682-50692 UBERON:0004529 denotes appendages
T25405 50704-50718 UBERON:0002073 denotes hair follicles
T25406 50723-50728 UBERON:0001091 denotes teeth
T25407 50743-50749 UBERON:0002370 denotes thymus
T25408 50743-50762 GO:0048538 denotes thymus organogensis
T25409 50784-50791 SO_EXT:0000704 denotes genetic
T25410 50806-50816 GO:0010467 denotes expression
T25411 50820-50823 PR_EXT:000004122 denotes Apc
T25412 50841-50851 GO:0065007 denotes regulation
T25413 50862-50866 CL_GO_EXT:cell denotes cell
T25414 50882-50888 UBERON:0000062 denotes organs
T25415 50902-50912 UBERON:0000483 denotes epithelial
T25416 50913-50924 UBERON:0003104 denotes mesenchymal
T26510 50979-50996 SO_EXT:0001644 denotes targeting vectors
T26511 51012-51015 PR_EXT:000004122 denotes Apc
T26512 51035-51038 SO_EXT:0000153 denotes BAC
T26513 51039-51044 SO_EXT:sequence_cloned_entity denotes clone
T26514 51079-51087 SO_EXT:biological_sequence denotes sequence
T26515 51091-51094 PR_EXT:000004122 denotes Apc
T26516 51110-51116 SO_EXT:0000204 denotes 5′ UTR
T26517 51121-51125 SO_EXT:0000147 denotes exon
T26518 51192-51201 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T26519 51225-51228 SO_EXT:0000153 denotes BAC
T26520 51241-51254 SO_EXT:sequence_alteration_entity_or_process denotes modifications
T26521 51275-51282 SO_EXT:0001026 denotes genomic
T26522 51283-51291 SO_EXT:biological_sequence denotes sequence
T26523 51305-51308 PR_EXT:000004122 denotes Apc
T26524 51309-51314 SO_EXT:0000147 denotes exons
T26525 51356-51362 SO_EXT:0000440 denotes vector
T26526 51375-51384 SO_EXT:0000346 denotes loxP site
T26527 51405-51411 SO_EXT:0000188 denotes intron
T26528 51427-51431 SO_EXT:0000346 denotes loxP
T26529 51432-51435 SO_EXT:0000350 denotes FRT
T26530 51436-51439 GO_EXT:phosphoglycerate_kinase denotes PGK
T26531 51439-51442 CHEBI_GO_EXT:neomycin_or_neomycin_phosphotransferase denotes neo
T26532 51439-51443 GO_EXT:0008910 denotes neor
T26533 51444-51447 SO_EXT:0000350 denotes FRT
T26534 51458-51466 SO_EXT:0005853 denotes cassette
T26535 51488-51491 PR_EXT:000004122 denotes Apc
T26536 51492-51496 SO_EXT:0000704 denotes gene
T27032 51511-51524 _FRAGMENT denotes Generation of
T27033 51535-51540 GO:0048468 denotes cells
T27034 51525-51528 PR_EXT:000004122 denotes Apc
T27035 51532-51540 CL:0002322 denotes ES cells
T27036 51535-51540 CL_GO_EXT:cell denotes cells
T27037 51545-51549 NCBITaxon:10088 denotes mice
T27038 51555-51565 SO_EXT:sequence_linearization denotes linearized
T27039 51566-51583 SO_EXT:0001644 denotes targeting vectors
T27040 51623-51631 CL:0002322 denotes ES cells
T27041 51626-51631 CL_GO_EXT:cell denotes cells
T27042 51637-51642 CL_GO_EXT:cell denotes cells
T27043 51663-51667 CHEBI:42768 denotes G418
T27044 51678-51680 CL:0002322 denotes ES
T27045 51681-51687 SO_EXT:sequence_cloned_entity denotes clones
T27046 51716-51720 SO_EXT:0000704 denotes gene
T27047 51866-51875 SO_EXT:sequence_insertion_entity_or_process denotes insertion
T27048 51890-51899 SO_EXT:0000346 denotes loxP site
T27049 51918-51926 SO_EXT:0005853 denotes cassette
T27050 51932-51934 CL:0002322 denotes ES
T27051 51935-51941 SO_EXT:sequence_cloned_entity denotes clones
T27052 51955-51958 PR_EXT:000004122 denotes Apc
T27053 51963-51964 SO_EXT:normal_or_wild_type_or_present denotes +
T27054 51965-51977 SO_EXT:sequence_alteration_entity_or_process denotes modification
T27055 52006-52017 UBERON:0000358 denotes blastocysts
T27056 52040-52044 NCBITaxon:10088 denotes mice
T27057 52065-52072 CL:0002322 denotes ES cell
T27058 52068-52072 CL_GO_EXT:cell denotes cell
T27059 52115-52122 PATO_UBERON_EXT:female_or_bearer_of_femaleness denotes females
T27060 52165-52176 SO_EXT:genomic_DNA denotes genomic DNA
T27061 52173-52176 CHEBI_SO_EXT:DNA denotes DNA
T27062 52203-52207 UBERON:0002415 denotes tail
T27063 52319-52332 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T27064 52363-52367 NCBITaxon:10088 denotes mice
T27065 52384-52388 NCBITaxon:10088 denotes mice
T27066 52395-52398 GO_EXT:phosphoglycerate_kinase denotes PGK
T27067 52398-52401 CHEBI_GO_EXT:neomycin_or_neomycin_phosphotransferase denotes neo
T27068 52398-52402 GO_EXT:0008910 denotes neor
T27069 52403-52411 SO_EXT:0005853 denotes cassette
T27070 52416-52423 SO_EXT:sequence_deletion_process denotes deleted
T27071 52443-52446 SO_EXT:0000350 denotes FRT
T27072 52456-52469 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T27073 52482-52486 NCBITaxon:10088 denotes mice
T27074 52502-52505 PR_EXT:000004122 denotes Apc
T27075 52509-52515 SO_EXT:0001023 denotes allele
T27076 52517-52520 PR_EXT:000004122 denotes Apc
T27077 52537-52541 NCBITaxon:10088 denotes mice
T27078 52587-52591 NCBITaxon:10088 denotes mice
T27079 52632-52636 GO_EXT:breeding denotes bred
T27416 52669-52672 PR_EXT:000004122 denotes Apc
T27417 52677-52681 NCBITaxon:10088 denotes mice
T27418 52683-52686 PR_EXT:000004122 denotes Apc
T27419 52703-52707 NCBITaxon:10088 denotes mice
T27420 52738-52742 NCBITaxon:10088 denotes mice
T27421 52753-52763 SO_EXT:transgenic_entity denotes transgenic
T27422 52764-52768 NCBITaxon:10088 denotes mice
T27423 52774-52781 GO:0010467 denotes express
T27424 52789-52801 UBERON:0019248 denotes early embryo
T27425 52824-52827 PR_EXT:000004122 denotes Apc
T27426 52828-52834 SO_EXT:0001023 denotes allele
T27427 52919-52922 PR_EXT:000004122 denotes Apc
T27428 52927-52928 SO_EXT:normal_or_wild_type_or_present denotes +
T27429 52929-52933 NCBITaxon:10088 denotes mice
T27430 52978-52985 PATO_UBERON_EXT:female_or_bearer_of_femaleness denotes females
T27671 53002-53005 PR_EXT:000009454 denotes K14
T27672 53011-53014 PR_EXT:000004122 denotes Apc
T27673 53022-53026 NCBITaxon:10088 denotes mice
T27674 53032-53036 NCBITaxon:10088 denotes mice
T27675 53087-53090 PR_EXT:000004122 denotes Apc
T27676 53107-53111 NCBITaxon:10088 denotes mice
T27677 53168-53171 PR_EXT:000009454 denotes K14
T27678 53176-53186 SO_EXT:transgenic_entity denotes transgenic
T27679 53187-53191 NCBITaxon:10088 denotes mice
T27680 53210-53213 PR_EXT:000009454 denotes K14
T27681 53219-53222 PR_EXT:000004122 denotes Apc
T27682 53226-53227 SO_EXT:normal_or_wild_type_or_present denotes +
T27683 53228-53232 PATO_UBERON_EXT:male_or_bearer_of_maleness denotes male
T27684 53233-53237 NCBITaxon:10088 denotes mice
T27685 53276-53279 PR_EXT:000004122 denotes Apc
T27686 53287-53294 PATO_UBERON_EXT:female_or_bearer_of_femaleness denotes females
T27687 53335-53338 PR_EXT:000004122 denotes Apc
T27688 53375-53378 PR_EXT:000009454 denotes K14
T27689 53388-53392 NCBITaxon:10088 denotes mice
T28229 53454-53458 NCBITaxon:10088 denotes mice
T28230 53460-53471 SO_EXT:genomic_DNA denotes Genomic DNA
T28231 53468-53471 CHEBI_SO_EXT:DNA denotes DNA
T28232 53477-53484 _FRAGMENT denotes tips of
T28233 53491-53496 UBERON:0010162 denotes tails
T28234 53485-53490 NCBITaxon:10088 denotes mouse
T28235 53580-53587 SO_EXT:0000112 denotes primers
T28236 53589-53592 PR_EXT:000004122 denotes Apc
T28237 53630-53633 PR_EXT:000004122 denotes Apc
T28238 53685-53687 SO_EXT:0000028 denotes bp
T28239 53696-53698 SO_EXT:0000028 denotes bp
T28240 53717-53726 SO_EXT:wild_type_entity_or_quality denotes wild-type
T28241 53743-53746 PR_EXT:000004122 denotes Apc
T28242 53750-53756 SO_EXT:0001023 denotes allele
T28243 53806-53813 SO_EXT:sequence_deletion_process denotes deleted
T28244 53814-53817 PR_EXT:000004122 denotes Apc
T28245 53818-53824 SO_EXT:0001023 denotes allele
T28246 53826-53829 PR_EXT:000004122 denotes Apc
T28247 53839-53845 SO_EXT:0000112 denotes primer
T28248 53846-53849 PR_EXT:000004122 denotes Apc
T28249 53903-53906 PR_EXT:000004122 denotes Apc
T28250 53931-53933 SO_EXT:0000028 denotes bp
T28251 53943-53950 SO_EXT:0000112 denotes Primers
T28252 54049-54058 SO_EXT:0000902 denotes transgene
T28253 54093-54095 SO_EXT:0000028 denotes bp
T28254 54169-54173 CHEBI:9754 denotes Tris
T28255 54174-54177 CHEBI:17883 denotes HCl
T28256 54194-54197 CHEBI:32588 denotes KCl
T28257 54206-54211 CHEBI:6636 denotes MgCl2
T28258 54220-54224 CHEBI_EXT:dNTP denotes dNTP
T28259 54240-54246 SO_EXT:0000112 denotes primer
T28260 54271-54275 CHEBI_EXT:gold denotes Gold
T28261 54405-54411 CHEBI_GO_SO_EXT:enzyme denotes enzyme
T28744 54546-54550 UBERON_EXT:zone_of_skin_or_skin_of_body denotes Skin
T28745 54606-54613 UBERON:0000922 denotes embryos
T28746 54655-54660 CHEBI:75055 denotes X-gal
T28747 54670-54673 CHEBI:60004 denotes mix
T28748 54692-54697 CHEBI:37586 denotes NaPO4
T28749 54706-54711 CHEBI:6636 denotes MgCl2
T28750 54718-54727 CHEBI:30060 denotes K3Fe(CN)6
T28751 54734-54743 CHEBI:30059 denotes K4Fe(CN)6
T28752 54757-54762 CHEBI:75055 denotes X-gal
T28753 54829-54838 UBERON:0007376 denotes epidermal
T28754 54852-54860 CHEBI:75958 denotes solution
T28755 54872-54881 UBERON:0007376 denotes epidermis
T28756 54900-54915 GO_EXT:0004565 denotes β-galactosidase
T28757 54930-54939 GO_MOP_EXT:catalysis denotes catalyzes
T28758 54990-54997 UBERON:0000922 denotes embryos
T28759 55054-55070 CHEBI_EXT:paraformaldehye denotes paraformaldehyde
T29058 55131-55139 UBERON:0004288 denotes Skeletal
T29059 55182-55188 UBERON_EXT:body denotes bodies
T29060 55216-55223 SO_EXT:sequence_altered_entity denotes mutants
T29061 55288-55307 CHEBI:32035 denotes potassium hydroxide
T29062 55309-55312 CHEBI:32035 denotes KOH
T29063 55327-55333 UBERON_EXT:body denotes bodies
T29064 55339-55350 GO_EXT:biological_movement_or_translocation_process denotes transferred
T29065 55364-55372 CHEBI:75958 denotes solution
T29066 55379-55382 CHEBI:32035 denotes KOH
T29067 55414-55426 CHEBI:16866 denotes alizarin red
T29068 55511-55517 UBERON_EXT:body denotes bodies
T29069 55533-55541 CHEBI:17754 denotes glycerin
T29465 55598-55604 UBERON:0000479 denotes tissue
T29466 55614-55627 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T29467 55629-55637 SO_EXT:genotype_or_entity_with_genotype denotes Genotype
T29468 55638-55644 UBERON:0000479 denotes tissue
T29469 55654-55667 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T29470 55687-55693 SO_EXT:0001023 denotes allele
T29471 55723-55725 GO_EXT:reverse_transcription_or_reverse_transcriptase denotes RT
T29472 55731-55734 CHEBI_SO_EXT:DNA denotes DNA
T29473 55766-55773 UBERON:0000479 denotes tissues
T29474 55853-55856 CHEBI_SO_EXT:RNA denotes RNA
T29475 55880-55886 UBERON:0000479 denotes tissue
T29476 55909-55916 CHEBI_EXT:33893 denotes reagent
T29477 55935-55945 GO:0010467 denotes expression
T29478 55949-55958 SO_EXT:wild_type_entity_or_quality denotes wild-type
T29479 55963-55972 SO_EXT:sequence_truncation_process denotes truncated
T29480 55973-55976 PR_EXT:000004122 denotes Apc
T29481 55977-55984 SO_EXT:0001023 denotes alleles
T29482 56009-56011 GO_EXT:reverse_transcription_or_reverse_transcriptase denotes RT
T29483 56021-56029 CHEBI_EXT:platinum denotes Platinum
T29484 56150-56153 CHEBI_SO_EXT:RNA denotes RNA
T29485 56166-56170 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T29486 56172-56177 UBERON:0002107 denotes liver
T29487 56182-56188 UBERON:0002370 denotes thymus
T29488 56199-56207 SO_EXT:genotype_or_entity_with_genotype denotes genotype
T29489 56212-56231 GO:0001171 denotes reverse-transcribed
T29490 56238-56245 SO_EXT:0000112 denotes primers
T29491 56246-56249 PR_EXT:000004122 denotes Apc
T29492 56283-56286 PR_EXT:000004122 denotes Apc
T29493 56334-56336 SO_EXT:0000028 denotes bp
T29494 56345-56347 SO_EXT:0000028 denotes bp
T29495 56366-56375 SO_EXT:wild_type_entity_or_quality denotes wild-type
T29496 56376-56379 PR_EXT:000004122 denotes Apc
T29497 56383-56390 SO_EXT:0001023 denotes alleles
T29498 56395-56398 PR_EXT:000004122 denotes Apc
T29499 56403-56409 SO_EXT:0001023 denotes allele
T29750 56426-56430 CHEBI:472552 denotes BrdU
T29751 56431-56439 CHEBI_SO_EXT:molecular_label_or_mark_or_tag_process denotes labeling
T29752 56441-56445 NCBITaxon:10088 denotes Mice
T29753 56465-56477 UBERON:0001179 denotes peritoneally
T29754 56505-56509 UBERON_EXT:body denotes body
T29755 56520-56524 CHEBI:472552 denotes BrdU
T29756 56567-56572 GO:0016265 denotes death
T29757 56574-56580 UBERON:0000479 denotes Tissue
T30401 56688-56694 SO_EXT:sequence_altered_entity_or_alteration_process denotes Mutant
T30402 56695-56699 NCBITaxon:10088 denotes mice
T30403 56743-56749 GO_EXT:killing denotes killed
T30404 56769-56772 CHEBI:16526 denotes CO2
T30405 56785-56789 NCBITaxon:10088 denotes Mice
T30406 56817-56821 UBERON_EXT:zone_of_skin_or_skin_of_body denotes skin
T30407 56856-56864 CHEBI_EXT:nitrogen denotes nitrogen
T30408 56902-56909 CHEBI_EXT:33893 denotes reagent
T30409 56937-56946 CHEBI_EXT:polyatomic_entity_or_group denotes molecular
T30410 57008-57016 CHEBI:75958 denotes solution
T30411 57076-57080 NCBITaxon:10088 denotes mice
T30412 57132-57139 UBERON:0000479 denotes tissues
T30413 57176-57185 CHEBI_EXT:polyatomic_entity_or_group denotes molecular
T30414 57209-57219 UBERON:0000468 denotes whole body
T30415 57241-57249 CHEBI:75958 denotes solution
T30416 57286-57292 NCBITaxon:9989 denotes Rodent
T30417 57416-57422 UBERON:0000479 denotes tissue
T30418 57454-57460 CHEBI:27338 denotes xylene
T30419 57474-57481 CHEBI:30879 denotes alcohol
T30420 57522-57533 GO_EXT:0004601 denotes peroxidases
T30421 57540-57544 CHEBI:16240 denotes H2O2
T30422 57548-57556 CHEBI:17790 denotes methanol
T30423 57594-57599 CHEBI:15377 denotes water
T30424 57608-57615 CHEBI_EXT:59132 denotes antigen
T30425 57702-57709 CHEBI_EXT:citrate denotes citrate
T30426 57710-57716 CHEBI_CHMO_EXT:buffer_solution denotes buffer
T30427 57771-57781 GO:0042571 denotes antibodies
T30428 57813-57823 GO:0042571 denotes Antibodies
T30429 57834-57843 PR_EXT:000002198 denotes β-catenin
T30430 57848-57860 GO:0009293 denotes Transduction
T30431 57905-57915 PR_EXT:000009450 denotes keratins 1
T30432 57905-57913 _FRAGMENT denotes keratins
T30433 57917-57918 PR_EXT:000009481 denotes 5
T30434 57920-57921 PR_EXT:keratin_6 denotes 6
T30435 57923-57925 PR_EXT:000009454 denotes 14
T30436 57927-57937 PR_EXT:000009167 denotes involucrin
T30437 57939-57947 PR_EXT:000009882 denotes loricrin
T30438 57996-58005 PR_EXT:000009495 denotes keratin 8
T30439 58042-58046 PR_EXT:000010425 denotes Ki67
T30440 58112-58116 CHEBI:472552 denotes BrdU
T30441 58126-58138 MOP:0000093 denotes Biotinylated
T30442 58149-58159 GO:0042571 denotes antibodies
T30443 58161-58167 NCBITaxon:9793 denotes donkey
T30444 58173-58179 NCBITaxon:9986 denotes rabbit
T30445 58184-58188 NCBITaxon:9925 denotes goat
T30446 58194-58199 NCBITaxon:10088 denotes mouse
T30447 58200-58203 GO:0071735 denotes IgG
T30448 58431-58442 CHEBI:51686 denotes hematoxylin
T30889 58453-58466 GO:0097617 denotes hybridization
T30890 58486-58489 NCBITaxon:10114 denotes rat
T30891 58490-58493 PR_EXT:000014841 denotes Shh
T30892 58494-58499 CHEBI_SO_EXT:molecular_probe denotes probe
T30893 58531-58540 PR_EXT:000002198 denotes β-catenin
T30894 58541-58546 CHEBI_SO_EXT:molecular_probe denotes probe
T30895 58600-58610 CHEBI_SO_EXT:riboprobe denotes Riboprobes
T30896 58611-58618 CHEBI_SO_EXT:molecular_label_or_mark_or_tag_process denotes labeled
T30897 58624-58627 CHEBI:42098 denotes DIG
T30898 58657-58659 GO_PR_EXT:alkaline_phosphatase denotes AP
T30899 58684-58692 CHEBI:75958 denotes solution
T2305 5354-5357 GO:0016265 denotes die
T25237 46474-46488 CL:0002365 denotes medullary TECs
R4 T500 T499 _lexicallyChainedTo Thymus,Development of
R5 T525 T524 _lexicallyChainedTo stratified epithelia,cells of
R6 T543 T542 _lexicallyChainedTo epithelia,oral
R241 T2214 T2213 _lexicallyChainedTo nucleus,migration to
R242 T2245 T2244 _lexicallyChainedTo cell cycle,regulation of
R243 T2246 T2244 _lexicallyChainedTo apoptosis,regulation of
R244 T2286 T2285 _lexicallyChainedTo organs,morphogenesis of
R245 T2336 T2335 _lexicallyChainedTo stratified epithelia,cells of
R246 T2343 T2342 _lexicallyChainedTo organs,development of
R912 T4439 T4438 _lexicallyChainedTo cells,embryonic stem
R913 T4439 T4440 _lexicallyChainedTo cells,ES
R914 T4451 T4450 _lexicallyChainedTo sites,FLP recognition target
R915 T4451 T4452 _lexicallyChainedTo sites,FRT
R916 T4471 T4470 _lexicallyChainedTo sites,loxP
R917 T4511 T4510 _lexicallyChainedTo reading frame,shift in
R1592 T7535 T7534 _lexicallyChainedTo epidermis,cells of
R1593 T7549 T7548 _lexicallyChainedTo thymus,medulla of
R1594 T7672 T7671 _lexicallyChainedTo molars,maxillary
R3040 T12358 T12357 _lexicallyChainedTo epidermis,basal layer of
R3041 T12371 T12370 _lexicallyChainedTo hair cycle,anagen phase of
R3042 T12413 T12412 _lexicallyChainedTo layers of epidermis,spinous
R3043 T12429 T12428 _lexicallyChainedTo hair follicle,ORS of
R3044 T12454 T12453 _lexicallyChainedTo hair follicles,ORS of
R3045 T12488 T12487 _lexicallyChainedTo cells,basal
R3046 T12560 T12559 _lexicallyChainedTo morphogenesis,embryonic
R4269 T14496 T14495 _lexicallyChainedTo salivary,epithelia of
R4270 T14497 T14496 _lexicallyChainedTo glands,salivary
R4271 T14498 T14495 _lexicallyChainedTo Hardarian glands,epithelia of
R4272 T14500 T14499 _lexicallyChainedTo glands,oral
R4558 T17016 T17015 _lexicallyChainedTo medulla,TECs of
R4559 T17021 T17020 _lexicallyChainedTo TEC,Cortical
R4560 T17108 T17107 _lexicallyChainedTo cells,populations of
R4561 T17166 T17165 _lexicallyChainedTo cells,keratinizing
R4562 T17187 T17186 _lexicallyChainedTo cells,keratinizing
R4563 T17233 T17232 _lexicallyChainedTo TECs,medullary
R5945 T21951 T21950 _lexicallyChainedTo stem cells,specification of
R5946 T21952 T21950 _lexicallyChainedTo ectodermal,specification of
R5947 T21953 T21952 _lexicallyChainedTo cells,ectodermal
R5948 T21956 T21955 _lexicallyChainedTo stem cells,embryonic
R5949 T21957 T21952 _lexicallyChainedTo cells,ectodermal
R5950 T22017 T22016 _lexicallyChainedTo morphogenesis,embryonic
R5951 T22058 T22057 _lexicallyChainedTo epidermis,basal cells of
R5952 T22061 T22060 _lexicallyChainedTo ORS of hair follicles,cells of
R5953 T22132 T22131 _lexicallyChainedTo development,embryonic
R7219 T25284 T25283 _lexicallyChainedTo TECs,medullary
R7220 T25358 T25357 _lexicallyChainedTo TECs,cortical
R8155 T27033 T27032 _lexicallyChainedTo cells,Generation of
R8501 T28233 T28232 _lexicallyChainedTo tails,tips of
R9144 T30433 T30432 _lexicallyChainedTo 5,keratins
R9145 T30434 T30432 _lexicallyChainedTo 6,keratins
R9146 T30435 T30432 _lexicallyChainedTo 14,keratins

craft-ca-core-dev

Below, discontinuous spans are shown in the chain model. You can change it to the bag model.

Id Subject Object Predicate Lexical cue
T435 0-26 PR:000004122 denotes Adenomatous Polyposis Coli
T436 28-31 PR:000004122 denotes APC
T437 56-75 GO:0043588 denotes Development of Skin
T438 56-70 _FRAGMENT denotes Development of
T439 80-86 GO:0048538 denotes Thymus
T440 80-86 UBERON:0002370 denotes Thymus
T441 157-161 SO:0000704 denotes gene
T442 162-165 PR:000004122 denotes Apc
T443 167-193 PR:000004122 denotes adenomatous polyposis coli
T444 214-235 GO:0016055 denotes Wnt signaling pathway
T445 309-313 NCBITaxon:10088 denotes mice
T446 318-321 PR:000004122 denotes Apc
T447 386-395 UBERON:0000922 denotes embryonic
T448 433-436 PR:000004122 denotes Apc
T449 467-473 SO:0000359 denotes floxed
T450 474-480 SO:0001023 denotes allele
T451 488-492 NCBITaxon:10088 denotes mice
T452 498-503 GO:0007618 denotes mated
T453 553-560 GO:0065007 denotes control
T454 568-573 NCBITaxon:9606 denotes human
T455 574-584 PR:000009454 denotes Keratin 14
T456 586-589 PR:000009454 denotes K14
T457 591-599 SO:0000167 denotes promoter
T458 620-644 CL:0002187 denotes basal cells of epidermis
T459 626-634 _FRAGMENT denotes cells of
T460 655-675 CL:0000079 denotes stratified epithelia
T461 635-644 UBERON:0007376 denotes epidermis
T462 655-675 UBERON:0000486 denotes stratified epithelia
T463 677-681 NCBITaxon:10088 denotes Mice
T464 701-707 SO:0000359 denotes floxed
T465 708-714 SO:0001023 denotes allele
T466 735-738 PR:000009454 denotes K14
T467 743-752 SO:0000902 denotes transgene
T468 792-796 GO:0016265 denotes died
T469 872-875 PR:000009454 denotes K14
T470 889-892 PR:000004122 denotes Apc
T471 934-946 UBERON:0000924 denotes ectodermally
T472 955-973 UBERON:0006914 denotes squamous epithelia
T473 985-999 UBERON:0002073 denotes hair follicles
T474 1001-1006 UBERON:0001091 denotes teeth
T475 1012-1016 _FRAGMENT denotes oral
T476 1029-1038 UBERON:0002424 denotes epithelia
T477 1021-1038 UBERON:0001772 denotes corneal epithelia
T478 1097-1107 UBERON:0000483 denotes epithelial
T479 1116-1123 UBERON:0000479 denotes tissues
T480 1139-1145 UBERON:0002370 denotes thymus
T481 1170-1184 UBERON:0002073 denotes hair follicles
T482 1195-1205 UBERON:0004529 denotes appendages
T483 1221-1227 UBERON:0002370 denotes thymic
T484 1245-1248 PR:000009454 denotes K14
T485 1254-1257 PR:000004122 denotes Apc
T486 1265-1269 NCBITaxon:10088 denotes mice
T487 1282-1285 PR:000004122 denotes Apc
T488 1286-1290 SO:0000704 denotes gene
T489 1305-1314 UBERON:0000922 denotes embryonic
T490 1305-1320 CL:0002321 denotes embryonic cells
T491 1332-1342 UBERON:0000483 denotes epithelial
T492 1332-1347 CL:0000066 denotes epithelial cell
T493 1357-1363 UBERON:0000062 denotes organs
T494 1377-1387 UBERON:0000483 denotes epithelial
T495 1388-1399 UBERON:0003104 denotes mesenchymal
T2063 2771-2797 PR:000004122 denotes Adenomatous polyposis coli
T2064 2799-2802 PR:000004122 denotes APC
T2065 2823-2844 GO:0016055 denotes Wnt signaling pathway
T2066 2882-2890 GO:0065007 denotes regulate
T2067 2905-2914 PR:000002198 denotes β-catenin
T2068 2931-2940 PR:000002198 denotes β-catenin
T2069 2941-2951 GO:0065007 denotes regulation
T2070 2971-2976 NCBITaxon:9606 denotes human
T2071 2997-3000 PR:000004122 denotes APC
T2072 3041-3050 GO:0005829 denotes cytosolic
T2073 3051-3060 PR:000002198 denotes β-catenin
T2074 3092-3104 _FRAGMENT denotes migration to
T2075 3109-3116 GO:0051170 denotes nucleus
T2076 3109-3116 GO:0005634 denotes nucleus
T2077 3178-3181 PR:000004122 denotes APC
T2078 3252-3258 PR:000004527 denotes axin-2
T2079 3260-3265 PR:000004527 denotes AXIN2
T2080 3268-3279 PR:000009235 denotes plakoglobin
T2081 3281-3284 PR:000009235 denotes JUP
T2082 3287-3291 PR:000004257 denotes Asef
T2083 3293-3300 PR:000004257 denotes ARHGEF4
T2084 3303-3343 PR:000009322 denotes kinesin superfamily–associated protein 3
T2085 3345-3351 PR:000009322 denotes KIFAP3
T2086 3354-3357 PR:000010170 denotes EB1
T2087 3359-3365 PR:000010170 denotes MAPRE1
T2088 3368-3380 GO:0005874 denotes microtubules
T2089 3390-3395 NCBITaxon:9606 denotes human
T2090 3396-3403 SO:0000853 denotes homolog
T2091 3396-3429 PR:000006511 denotes homolog of Drosophila discs large
T2092 3407-3417 NCBITaxon:7215 denotes Drosophila
T2093 3431-3435 PR:000006511 denotes DLG1
T2094 3470-3473 PR:000004122 denotes APC
T2095 3490-3498 GO:0065007 denotes regulate
T2096 3558-3570 GO:0005856 denotes cytoskeletal
T2097 3585-3595 GO:0065007 denotes regulation
T2098 3599-3610 PR:000009235 denotes plakoglobin
T2099 3619-3632 _FRAGMENT denotes regulation of
T2100 3637-3647 GO:0051726 denotes cell cycle
T2101 3652-3661 GO:0042981 denotes apoptosis
T2102 3678-3707 GO:0098722 denotes asymmetric stem cell division
T2103 3689-3698 CL:0000034 denotes stem cell
T2104 3713-3741 GO:2000114 denotes control of cell polarization
T2105 3749-3752 PR:000004122 denotes APC
T2106 3775-3779 SO:0000704 denotes gene
T2107 3802-3805 PR:000004122 denotes APC
T2108 3858-3863 UBERON:0001155 denotes colon
T2109 3868-3874 UBERON:0001052 denotes rectum
T2110 3876-3885 GO:0030849 denotes Autosomal
T2111 3917-3920 PR:000004122 denotes APC
T2112 4056-4066 UBERON:0012652 denotes colorectal
T2113 4116-4126 UBERON:0012652 denotes colorectal
T2114 4169-4173 UBERON:0000104 denotes life
T2115 4196-4206 UBERON:0012652 denotes colorectal
T2116 4223-4234 NCBITaxon:1 denotes individuals
T2117 4252-4259 UBERON:0001155 denotes colonic
T2118 4292-4314 UBERON:0001555 denotes gastrointestinal tract
T2119 4353-4379 UBERON:0001782 denotes retinal pigment epithelium
T2120 4361-4368 CHEBI:26130 denotes pigment
T2121 4414-4423 UBERON:0002397 denotes maxillary
T2122 4428-4436 UBERON:0004288 denotes skeletal
T2123 4437-4442 UBERON:0001474 denotes bones
T2124 4448-4454 UBERON:0001091 denotes dental
T2125 4503-4506 PR:000004122 denotes APC
T2126 4507-4511 SO:0000704 denotes gene
T2127 4531-4544 UBERON:0000467 denotes organ systems
T2128 4567-4570 PR:000004122 denotes APC
T2129 4592-4597 NCBITaxon:9606 denotes human
T2130 4598-4608 UBERON:0012652 denotes colorectal
T2131 4655-4661 UBERON:0000479 denotes tissue
T2132 4739-4766 GO:0030111 denotes regulation of Wnt signaling
T2133 4770-4779 UBERON:0000922 denotes embryonic
T2134 4770-4797 GO:0009880 denotes embryonic pattern formation
T2135 4802-4818 _FRAGMENT denotes morphogenesis of
T2136 4824-4830 GO:0009887 denotes organs
T2137 4824-4830 UBERON:0000062 denotes organs
T2138 4861-4864 PR:000004122 denotes APC
T2139 4892-4899 UBERON:0001155 denotes colonic
T2140 4900-4907 UBERON:0000479 denotes tissues
T2141 4970-4976 NCBITaxon:9606 denotes humans
T2142 5017-5020 PR:000004122 denotes Apc
T2143 5050-5054 NCBITaxon:10088 denotes mice
T2144 5076-5079 PR:000004122 denotes Apc
T2145 5098-5109 SO:0000704 denotes genetically
T2146 5119-5124 NCBITaxon:10088 denotes mouse
T2147 5137-5140 PR:000004122 denotes Apc
T2148 5225-5241 UBERON:0005409 denotes gastrointestinal
T2149 5291-5296 NCBITaxon:10088 denotes Mouse
T2150 5297-5304 UBERON:0000922 denotes embryos
T2151 5333-5340 SO:0000704 denotes genetic
T2152 5354-5357 GO:0016265 denotes die
T2153 5365-5378 GO:0009790 denotes embryogenesis
T2154 5425-5437 GO:0007369 denotes gastrulation
T2155 5494-5497 PR:000004122 denotes Apc
T2156 5532-5539 UBERON:0000479 denotes tissues
T2157 5557-5562 NCBITaxon:10088 denotes mouse
T2158 5608-5614 SO:0001023 denotes allele
T2159 5619-5623 GO:0007618 denotes mate
T2160 5634-5639 NCBITaxon:10088 denotes mouse
T2161 5700-5706 SO:0001023 denotes allele
T2162 5756-5759 PR:000004122 denotes Apc
T2163 5773-5787 UBERON:0000105 denotes stages of life
T2164 5817-5821 NCBITaxon:10088 denotes mice
T2165 5869-5875 SO:0001023 denotes allele
T2166 5879-5882 PR:000004122 denotes Apc
T2167 5884-5887 PR:000004122 denotes Apc
T2168 5899-5903 NCBITaxon:10088 denotes mice
T2169 5909-5914 GO:0007618 denotes mated
T2170 5964-5971 GO:0065007 denotes control
T2171 5979-5984 NCBITaxon:9606 denotes human
T2172 5985-5995 PR:000009454 denotes Keratin 14
T2173 5997-6000 PR:000009454 denotes K14
T2174 6002-6010 SO:0000167 denotes promoter
T2175 6031-6055 CL:0002187 denotes basal cells of epidermis
T2176 6037-6045 _FRAGMENT denotes cells of
T2177 6066-6086 CL:0000079 denotes stratified epithelia
T2178 6046-6055 UBERON:0007376 denotes epidermis
T2179 6066-6086 UBERON:0000486 denotes stratified epithelia
T2180 6108-6111 PR:000009454 denotes K14
T2181 6112-6120 SO:0000167 denotes promoter
T2182 6136-6139 PR:000004122 denotes Apc
T2183 6161-6175 _FRAGMENT denotes development of
T2184 6184-6190 GO:0048513 denotes organs
T2185 6184-6190 UBERON:0000062 denotes organs
T2186 6214-6224 UBERON:0000483 denotes epithelial
T2187 6225-6236 UBERON:0003104 denotes mesenchymal
T2188 6261-6274 UBERON:0002073 denotes hair follicle
T2189 6276-6281 UBERON:0001091 denotes teeth
T2190 6287-6293 UBERON:0002370 denotes thymus
T2191 6320-6325 GO:0016265 denotes death
T2192 6329-6333 NCBITaxon:10088 denotes mice
T2193 6349-6352 PR:000004122 denotes Apc
T2194 6377-6405 GO:0001709 denotes determinations of cell fates
T2195 6417-6426 UBERON:0000922 denotes embryonic
T2196 6417-6438 GO:0009790 denotes embryonic development
T2197 6466-6472 UBERON:0000479 denotes tissue
T2198 6482-6492 GO:0065007 denotes regulation
T2199 6496-6505 PR:000002198 denotes β-catenin
T2200 6530-6540 UBERON:0004529 denotes appendages
T2201 6553-6559 UBERON:0002370 denotes thymus
T4305 6608-6612 NCBITaxon:10088 denotes Mice
T4306 6640-6643 PR:000004122 denotes Apc
T4307 6647-6666 GO:0043588 denotes development of skin
T4308 6675-6685 UBERON:0004529 denotes appendages
T4309 6703-6707 SO:0000346 denotes loxP
T4310 6762-6765 PR:000004122 denotes Apc
T4311 6766-6770 SO:0000704 denotes gene
T4312 6774-6778 NCBITaxon:10088 denotes mice
T4313 6795-6804 UBERON:0000922 denotes embryonic
T4314 6795-6809 _FRAGMENT denotes embryonic stem
T4315 6815-6820 CL:0002322 denotes cells
T4316 6811-6813 _FRAGMENT denotes ES
T4317 6825-6829 NCBITaxon:10088 denotes mice
T4318 6842-6845 PR:000004122 denotes Apc
T4319 6846-6852 SO:0001023 denotes allele
T4320 6878-6888 SO:0000346 denotes loxP sites
T4321 6889-6897 SO:0000357 denotes flanking
T4322 6898-6901 PR:000004122 denotes Apc
T4323 6902-6906 SO:0000147 denotes exon
T4324 6924-6927 PR:P03870 denotes FLP
T4325 6924-6946 _FRAGMENT denotes FLP recognition target
T4326 6953-6958 SO:0000350 denotes sites
T4327 6948-6951 _FRAGMENT denotes FRT
T4328 6959-6967 SO:0000357 denotes flanking
T4329 6972-6980 CHEBI:7507 denotes neomycin
T4330 6991-6999 SO:0005853 denotes cassette
T4331 7038-7041 PR:000004122 denotes Apc
T4332 7046-7052 SO:0001023 denotes allele
T4333 7060-7068 CHEBI:7507 denotes neomycin
T4334 7069-7077 SO:0005853 denotes cassette
T4335 7086-7094 CHEBI:7507 denotes neomycin
T4336 7095-7103 SO:0005853 denotes cassette
T4337 7160-7163 PR:000004122 denotes Apc
T4338 7167-7173 SO:0000188 denotes intron
T4339 7195-7199 SO:0000704 denotes gene
T4340 7205-7209 _FRAGMENT denotes loxP
T4341 7218-7223 SO:0000346 denotes sites
T4342 7214-7223 SO:0000350 denotes FRT sites
T4343 7283-7288 NCBITaxon:10088 denotes mouse
T4344 7364-7366 CL:0002322 denotes ES
T4345 7435-7438 PR:000004122 denotes Apc
T4346 7445-7449 NCBITaxon:10088 denotes mice
T4347 7493-7496 PR:000004122 denotes Apc
T4348 7502-7506 NCBITaxon:10088 denotes mice
T4349 7544-7547 PR:000004122 denotes Apc
T4350 7561-7564 PR:000004122 denotes Apc
T4351 7569-7575 SO:0001023 denotes allele
T4352 7597-7605 CHEBI:7507 denotes neomycin
T4353 7606-7614 SO:0005853 denotes cassette
T4354 7637-7647 SO:0000346 denotes loxP sites
T4355 7655-7662 SO:0000188 denotes introns
T4356 7663-7671 SO:0000357 denotes flanking
T4357 7672-7676 SO:0000147 denotes exon
T4358 7714-7718 SO:0000147 denotes exon
T4359 7725-7729 NCBITaxon:10088 denotes mice
T4360 7745-7748 PR:000004122 denotes Apc
T4361 7754-7758 NCBITaxon:10088 denotes mice
T4362 7835-7838 PR:000004122 denotes Apc
T4363 7851-7854 PR:000004122 denotes Apc
T4364 7873-7879 SO:0001023 denotes allele
T4365 7881-7884 PR:000004122 denotes Apc
T4366 7896-7900 SO:0000147 denotes exon
T4367 7921-7931 SO:0000673 denotes transcript
T4368 7945-7949 SO:0000147 denotes exon
T4369 7986-7999 SO:0000717 denotes reading frame
T4370 8016-8049 SO:0001587 denotes premature chain termination codon
T4371 8187-8190 PR:000004122 denotes Apc
T4372 9791-9795 UBERON:0002415 denotes tail
T4373 9826-9829 PR:000004122 denotes Apc
T4374 9838-9841 PR:000004122 denotes Apc
T4375 9900-9903 PR:000004122 denotes Apc
T4376 9904-9910 SO:0001023 denotes allele
T4377 9924-9928 NCBITaxon:10088 denotes Mice
T4378 9955-9958 PR:000004122 denotes Apc
T4379 10016-10024 UBERON:0000104 denotes lifespan
T4380 10079-10083 SO:0000147 denotes exon
T4381 10145-10148 PR:000004122 denotes Apc
T4382 10149-10153 SO:0000704 denotes gene
T4383 10163-10166 PR:000004122 denotes Apc
T4384 10173-10177 NCBITaxon:10088 denotes mice
T4385 10253-10259 UBERON:0001052 denotes rectal
T4386 10345-10348 PR:000004122 denotes Apc
T4387 10367-10372 NCBITaxon:10088 denotes mouse
T4388 10386-10389 PR:000004122 denotes Apc
T4389 10396-10400 NCBITaxon:10088 denotes mice
T4390 10438-10448 UBERON:0000160 denotes intestinal
T4391 10477-10482 GO:0016265 denotes death
T4392 10522-10525 PR:000004122 denotes Apc
T4393 10593-10603 UBERON:0000160 denotes intestinal
T4394 10616-10619 PR:000004122 denotes Apc
T4395 10626-10630 NCBITaxon:10088 denotes mice
T4396 10661-10672 GO:0006412 denotes translation
T4397 10714-10717 PR:000004122 denotes Apc
T4398 10802-10805 PR:000004122 denotes Apc
T4399 10825-10832 SO:0001023 denotes allelic
T4400 10850-10856 SO:0001023 denotes allele
T4401 10907-10911 NCBITaxon:10088 denotes mice
T4402 10916-10919 PR:000004122 denotes Apc
T4403 10985-10990 GO:0001967 denotes nurse
T4404 11037-11040 PR:000004122 denotes Apc
T4405 11046-11050 NCBITaxon:10088 denotes mice
T4406 11081-11084 PR:000004122 denotes Apc
T4407 11181-11184 PR:000004122 denotes Apc
T4408 11188-11194 SO:0001023 denotes allele
T4409 11202-11206 NCBITaxon:10088 denotes mice
T4410 11231-11235 NCBITaxon:10088 denotes mice
T4411 11240-11243 PR:000004122 denotes Apc
T4412 11247-11253 SO:0001023 denotes allele
T4413 11371-11374 PR:000004122 denotes Apc
T4414 11378-11384 SO:0001023 denotes allele
T4415 11414-11420 SO:0001023 denotes allele
T4416 11437-11440 PR:000004122 denotes Apc
T4417 11460-11463 PR:000004122 denotes Apc
T4418 11475-11480 NCBITaxon:10088 denotes mouse
T4419 11496-11499 PR:000004122 denotes Apc
T4420 11534-11538 GO:0007567 denotes born
T4421 11595-11605 SO:0000346 denotes loxP sites
T4422 11609-11616 SO:0000188 denotes introns
T4423 11617-11625 SO:0000357 denotes flanking
T4424 11626-11630 SO:0000147 denotes exon
T4425 11680-11683 PR:000004122 denotes Apc
T4426 11684-11688 SO:0000704 denotes gene
T7376 11691-11694 PR:000009454 denotes K14
T7377 11710-11713 PR:000004122 denotes Apc
T7378 11800-11803 PR:000004122 denotes Apc
T7379 11815-11825 GO:0010467 denotes expressing
T7380 11826-11829 PR:000009454 denotes K14
T7381 11846-11853 CL:0002322 denotes ES cell
T7382 11867-11870 PR:000004122 denotes Apc
T7383 11876-11880 NCBITaxon:10088 denotes mice
T7384 11886-11889 PR:000009454 denotes K14
T7385 11906-11910 NCBITaxon:10088 denotes mice
T7386 11939-11942 PR:000009454 denotes K14
T7387 11948-11951 PR:000004122 denotes Apc
T7388 11957-11961 NCBITaxon:10088 denotes mice
T7389 12006-12009 PR:000009454 denotes K14
T7390 12015-12018 PR:000004122 denotes Apc
T7391 12046-12049 PR:000004122 denotes Apc
T7392 12106-12113 CL:0000023 denotes oocytes
T7393 12117-12120 PR:000009454 denotes K14
T7394 12152-12156 NCBITaxon:10088 denotes mice
T7395 12214-12218 NCBITaxon:10088 denotes mice
T7396 12352-12355 PR:000009454 denotes K14
T7397 12356-12364 SO:0000167 denotes promoter
T7398 12384-12393 UBERON:0007376 denotes epidermal
T7399 12384-12398 CL:0000362 denotes epidermal cell
T7400 12399-12407 SO:0000167 denotes promoter
T7401 12423-12433 GO:0010467 denotes expression
T7402 12441-12452 GO:0007067 denotes mitotically
T7403 12460-12468 _FRAGMENT denotes cells of
T7404 12473-12482 CL:0000362 denotes epidermis
T7405 12473-12482 UBERON:0007376 denotes epidermis
T7406 12491-12501 UBERON:0004529 denotes appendages
T7407 12556-12574 UBERON:0000924 denotes embryonic ectoderm
T7408 12606-12616 UBERON:0000924 denotes ectodermal
T7409 12626-12635 UBERON:0000922 denotes embryonic
T7410 12667-12677 GO:0010467 denotes expression
T7411 12681-12684 PR:000009454 denotes K14
T7412 12702-12719 UBERON:0003846 denotes thymic epithelial
T7413 12702-12725 CL:0002293 denotes thymic epithelial cells
T7414 12727-12731 CL:0002293 denotes TECs
T7415 12740-12750 _FRAGMENT denotes medulla of
T7416 12758-12764 UBERON:0002124 denotes thymus
T7417 12864-12867 PR:000009454 denotes K14
T7418 12873-12876 PR:000004122 denotes Apc
T7419 12886-12889 PR:000004122 denotes Apc
T7420 12897-12901 NCBITaxon:10088 denotes mice
T7421 12914-12918 NCBITaxon:10088 denotes mice
T7422 12935-12938 PR:000009454 denotes K14
T7423 12944-12947 PR:000004122 denotes Apc
T7424 12983-12987 GO:0007567 denotes born
T7425 13214-13219 GO:0007567 denotes birth
T7426 13307-13311 GO:0007567 denotes born
T7427 13370-13373 PR:000009454 denotes K14
T7428 13379-13382 PR:000004122 denotes Apc
T7429 13437-13441 GO:0007567 denotes born
T7430 13499-13505 GO:0001967 denotes nursed
T7431 13530-13534 UBERON:0001913 denotes milk
T7432 13544-13552 UBERON:0000945 denotes stomachs
T7433 13585-13590 GO:0007567 denotes birth
T7434 13637-13642 GO:0007567 denotes natal
T7435 13782-13786 GO:0016265 denotes died
T7436 15267-15274 UBERON:0000922 denotes embryos
T7437 15291-15294 CHEBI:37958 denotes dye
T7438 15319-15328 UBERON:0007376 denotes epidermal
T7439 15479-15482 CHEBI:37958 denotes dye
T7440 15504-15513 UBERON:0007376 denotes epidermal
T7441 15555-15564 UBERON:0000922 denotes embryonic
T7442 15724-15733 UBERON:0008200 denotes foreheads
T7443 15780-15784 UBERON:0000033 denotes head
T7444 15788-15792 UBERON:0002415 denotes tail
T7445 15800-15813 UBERON:0001691 denotes external ears
T7446 15817-15823 UBERON:0001757 denotes pinnae
T7447 15857-15866 CHEBI:26130 denotes pigmented
T7448 15983-15988 GO:0007567 denotes birth
T7449 16023-16027 GO:0040007 denotes grew
T7450 16054-16065 UBERON:0010509 denotes pelage hair
T7451 16138-16142 UBERON:0001037 denotes hair
T7452 16233-16245 UBERON:0010166 denotes coat of hair
T7453 16276-16290 UBERON:0003451 denotes lower incisors
T7454 16388-16395 NCBITaxon:33208 denotes Animals
T7455 16482-16491 UBERON:0006378 denotes vibrissae
T7456 16510-16522 UBERON:0010509 denotes pelage hairs
T7457 16610-16614 UBERON:0001690 denotes ears
T7458 16616-16623 UBERON:0001711 denotes eyelids
T7459 16625-16633 UBERON:0008200 denotes forehead
T7460 16635-16639 UBERON:0000004 denotes nose
T7461 16720-16727 NCBITaxon:33208 denotes animals
T7462 16746-16750 UBERON:0000970 denotes eyes
T7463 17050-17055 UBERON:0001091 denotes tooth
T7464 17069-17077 UBERON:0001098 denotes incisors
T7465 17081-17087 UBERON:0003655 denotes molars
T7466 17099-17107 UBERON:0000945 denotes stomachs
T7467 17149-17153 CHEBI:33290 denotes food
T7468 17268-17274 GO:0007631 denotes ingest
T7469 17281-17285 CHEBI:33290 denotes food
T7470 17352-17356 UBERON:0001037 denotes hair
T7471 17580-17585 GO:0016265 denotes death
T7472 17620-17624 GO:0007567 denotes born
T7473 17635-17639 GO:0016265 denotes died
T7474 17816-17819 PR:000004122 denotes Apc
T7475 17854-17861 SO:0000704 denotes genetic
T7476 17943-17949 UBERON:0000062 denotes organs
T7477 17980-17985 UBERON:0002370 denotes thymi
T7478 18197-18202 UBERON:0002370 denotes thymi
T7479 18221-18225 NCBITaxon:10088 denotes mice
T7480 18267-18273 UBERON:0000479 denotes tissue
T7481 18301-18305 NCBITaxon:10088 denotes mice
T7482 18333-18341 UBERON:0004288 denotes skeletal
T7483 18369-18377 UBERON:0004288 denotes skeletal
T7484 18399-18403 NCBITaxon:10088 denotes mice
T7485 18417-18429 CHEBI:16866 denotes Alizarin red
T7486 18479-18483 NCBITaxon:10088 denotes mice
T7487 18491-18506 UBERON:0001684 denotes mandibular bone
T7488 18539-18543 NCBITaxon:10088 denotes mice
T7489 18580-18598 UBERON:0003450 denotes maxillary incisors
T7490 18580-18589 _FRAGMENT denotes maxillary
T7491 18603-18609 UBERON:0003666 denotes molars
T7492 18650-18658 UBERON:0004288 denotes skeletal
T9452 18689-18695 UBERON:0000479 denotes Tissue
T9453 18705-18715 GO:0010467 denotes Expression
T9454 18733-18736 PR:000004122 denotes Apc
T9455 18737-18748 SO:0000673 denotes Transcripts
T9456 18788-18791 PR:000009454 denotes K14
T9457 18860-18863 PR:000004122 denotes Apc
T9458 18865-18868 PR:000004122 denotes Apc
T9459 18874-18881 SO:0001023 denotes alleles
T9460 18883-18890 SO:0001026 denotes Genomic
T9461 18914-18919 UBERON:0002107 denotes liver
T9462 18921-18927 UBERON:0002370 denotes thymus
T9463 18969-18972 PR:000009454 denotes K14
T9464 18978-18981 PR:000004122 denotes Apc
T9465 18990-18993 PR:000009454 denotes K14
T9466 18999-19002 PR:000004122 denotes Apc
T9467 19009-19012 PR:000004122 denotes Apc
T9468 19025-19028 PR:000004122 denotes Apc
T9469 19049-19056 SO:0001026 denotes genomic
T9470 19072-19079 UBERON:0000479 denotes tissues
T9471 19096-19099 PR:000004122 denotes Apc
T9472 19104-19110 SO:0001023 denotes allele
T9473 19116-19118 SO:0000028 denotes bp
T9474 19164-19170 UBERON:0002370 denotes thymus
T9475 19178-19181 PR:000009454 denotes K14
T9476 19195-19199 NCBITaxon:10088 denotes mice
T9477 19224-19227 PR:000004122 denotes Apc
T9478 19228-19234 SO:0001023 denotes allele
T9479 19242-19248 UBERON:0002370 denotes thymus
T9480 19252-19255 PR:000009454 denotes K14
T9481 19261-19264 PR:000004122 denotes Apc
T9482 19270-19274 NCBITaxon:10088 denotes mice
T9483 19341-19347 NCBITaxon:33208 denotes animal
T9484 19357-19364 UBERON:0000479 denotes tissues
T9485 19450-19455 UBERON:0002107 denotes liver
T9486 19459-19462 PR:000009454 denotes K14
T9487 19493-19496 PR:000009454 denotes K14
T9488 19510-19515 NCBITaxon:10088 denotes mouse
T9489 19516-19523 UBERON:0000479 denotes tissues
T9490 19601-19607 UBERON:0000479 denotes tissue
T9491 19631-19635 NCBITaxon:10088 denotes mice
T9492 19651-19654 PR:000009454 denotes K14
T9493 20243-20246 PR:000004122 denotes Apc
T9494 20247-20258 SO:0000673 denotes transcripts
T9495 20293-20300 SO:0000112 denotes primers
T9496 20310-20314 SO:0000147 denotes exon
T9497 20378-20384 UBERON:0000479 denotes tissue
T9498 20422-20433 SO:0000006 denotes PCR product
T9499 20439-20441 SO:0000028 denotes bp
T9500 20462-20465 PR:000004122 denotes Apc
T9501 20467-20470 PR:000004122 denotes Apc
T9502 20476-20482 SO:0001023 denotes allele
T9503 20495-20502 UBERON:0000479 denotes tissues
T9504 20540-20549 GO:0010467 denotes expressed
T9505 20557-20560 PR:000009454 denotes K14
T9506 20574-20578 NCBITaxon:10088 denotes mice
T9507 20633-20636 PR:000009454 denotes K14
T9508 20650-20655 NCBITaxon:10088 denotes mouse
T9509 20656-20663 UBERON:0000479 denotes tissues
T9510 20679-20684 UBERON:0002107 denotes liver
T9511 20688-20691 PR:000009454 denotes K14
T9512 20705-20709 NCBITaxon:10088 denotes mice
T9513 20751-20757 SO:0001023 denotes allele
T9514 20763-20765 SO:0000028 denotes bp
T9515 20878-20884 UBERON:0000479 denotes tissue
T12193 20929-20932 PR:000009454 denotes K14
T12194 20944-20947 PR:000004122 denotes Apc
T12195 20970-20984 UBERON:0002073 denotes Hair Follicles
T12196 21000-21009 UBERON:0007376 denotes Epidermis
T12197 21059-21063 UBERON:0001037 denotes hair
T12198 21175-21188 UBERON:0002073 denotes hair follicle
T12199 21195-21204 UBERON:0007376 denotes epidermal
T12200 21205-21214 UBERON:0004529 denotes appendage
T12201 21306-21310 UBERON:0001037 denotes hair
T12202 21324-21341 UBERON:0005942 denotes outer root sheath
T12203 21343-21346 UBERON:0005942 denotes ORS
T12204 21400-21414 _FRAGMENT denotes basal layer of
T12205 21419-21428 UBERON:0002025 denotes epidermis
T12206 21454-21467 UBERON:0002073 denotes hair follicle
T12207 21503-21520 UBERON:0005941 denotes inner root sheath
T12208 21552-21556 UBERON:0001037 denotes hair
T12209 21593-21606 UBERON:0002073 denotes hair follicle
T12210 21626-21644 UBERON:0005932 denotes hair follicle bulb
T12211 21669-21682 GO:0008283 denotes proliferating
T12212 21754-21771 UBERON:0005941 denotes inner root sheath
T12213 21780-21790 UBERON:0002074 denotes hair shaft
T12214 21815-21830 _FRAGMENT denotes anagen phase of
T12215 21835-21845 GO:0042640 denotes hair cycle
T12216 21835-21839 UBERON:0001037 denotes hair
T12217 21859-21873 UBERON:0002073 denotes hair follicles
T12218 21899-21903 NCBITaxon:10088 denotes mice
T12219 21904-21908 GO:0040007 denotes grew
T12220 21925-21941 UBERON:0002190 denotes subcutaneous fat
T12221 22236-22240 NCBITaxon:10088 denotes mice
T12222 22261-22265 UBERON:0010166 denotes coat
T12223 22518-22527 UBERON:0007376 denotes epidermis
T12224 22627-22641 UBERON:0002073 denotes hair follicles
T12225 22846-22850 UBERON:0010166 denotes coat
T12226 22867-22871 NCBITaxon:10088 denotes mice
T12227 23777-23780 PR:000004122 denotes Apc
T12228 23799-23808 PR:000002198 denotes β-catenin
T12229 23831-23844 GO:0016055 denotes Wnt signaling
T12230 23874-23884 GO:0010467 denotes expression
T12231 23888-23897 PR:000002198 denotes β-catenin
T12232 23914-23921 UBERON:0000479 denotes tissues
T12233 23943-23952 PR:000002198 denotes β-catenin
T12234 23970-23995 GO:0005912 denotes adherens junction complex
T12235 24014-24035 UBERON:0005942 denotes ORS of hair follicles
T12236 24040-24064 UBERON:0002025 denotes basal layer of epidermis
T12237 24072-24075 PR:000009454 denotes K14
T12238 24076-24086 GO:0010467 denotes expression
T12239 24136-24146 GO:0010467 denotes expression
T12240 24150-24152 PR:000009450 denotes K1
T12241 24154-24164 PR:000009167 denotes involucrin
T12242 24170-24178 PR:000009882 denotes loricrin
T12243 24192-24199 _FRAGMENT denotes spinous
T12244 24213-24232 UBERON:0002026 denotes layers of epidermis
T12245 24204-24232 UBERON:0002069 denotes granular layers of epidermis
T12246 24268-24277 UBERON:0007376 denotes epidermis
T12247 24314-24324 GO:0010467 denotes expression
T12248 24328-24331 PR:000009454 denotes K14
T12249 24333-24335 PR:000009450 denotes K1
T12250 24337-24347 PR:000009167 denotes involucrin
T12251 24353-24361 PR:000009882 denotes loricrin
T12252 24405-24409 NCBITaxon:10088 denotes mice
T12253 24536-24546 GO:0010467 denotes expression
T12254 24577-24586 GO:0010467 denotes expressed
T12255 24627-24633 _FRAGMENT denotes ORS of
T12256 24638-24651 UBERON:0005942 denotes hair follicle
T12257 24667-24676 UBERON:0007376 denotes epidermis
T12258 24756-24770 UBERON:0002073 denotes hair follicles
T12259 24940-24943 UBERON:0005942 denotes ORS
T12260 24992-24995 PR:000009454 denotes K14
T12261 24999-25001 PR:000009481 denotes K5
T12262 25038-25051 GO:0008283 denotes proliferating
T12263 25086-25110 UBERON:0002025 denotes basal layer of epidermis
T12264 25129-25148 UBERON:0005932 denotes hair follicle bulbs
T12265 25201-25205 CHEBI:472552 denotes BrdU
T12266 25223-25227 PR:000010425 denotes Ki67
T12267 25228-25238 GO:0010467 denotes expression
T12268 25298-25311 UBERON:0002073 denotes hair follicle
T12269 25376-25382 _FRAGMENT denotes ORS of
T12270 25396-25410 UBERON:0005942 denotes hair follicles
T12271 25469-25487 UBERON:0005932 denotes hair follicle bulb
T12272 25499-25512 GO:0008283 denotes proliferating
T12273 25578-25591 GO:0008283 denotes proliferation
T12274 25703-25722 UBERON:0005932 denotes hair follicle bulbs
T12275 25872-25880 GO:0016020 denotes membrane
T12276 25941-25950 GO:0005829 denotes cytosolic
T12277 25951-25960 PR:000002198 denotes β-catenin
T12278 26040-26049 PR:000002198 denotes β-catenin
T12279 26050-26060 GO:0010467 denotes expressing
T12280 26094-26107 GO:0008283 denotes proliferating
T12281 26226-26235 GO:0005829 denotes cytosolic
T12282 26236-26245 PR:000002198 denotes β-catenin
T12283 26285-26288 PR:000009454 denotes K14
T12284 26298-26300 PR:000009450 denotes K1
T12285 26310-26325 UBERON:0002025 denotes basal epidermis
T12286 26329-26332 PR:000009454 denotes K14
T12287 26354-26359 _FRAGMENT denotes basal
T12288 26364-26369 CL:0000646 denotes cells
T12289 26360-26363 UBERON:0005942 denotes ORS
T12290 26360-26369 CL:0002561 denotes ORS cells
T12291 26393-26406 GO:0008283 denotes proliferating
T12292 26445-26458 UBERON:0002073 denotes hair follicle
T12293 26445-26472 GO:0031069 denotes hair follicle morphogenesis
T12294 26507-26517 GO:0010467 denotes expression
T12295 26529-26543 PR:000014841 denotes Sonic hedgehog
T12296 26545-26548 PR:000014841 denotes Shh
T12297 26560-26569 GO:0010467 denotes expressed
T12298 26573-26583 UBERON:0005932 denotes hair bulbs
T12299 26587-26596 UBERON:0000922 denotes embryonic
T12300 26627-26640 UBERON:0002073 denotes hair follicle
T12301 26627-26654 GO:0031069 denotes hair follicle morphogenesis
T12302 26694-26703 UBERON:0000922 denotes embryonic
T12303 26733-26743 GO:0010467 denotes expression
T12304 26747-26750 PR:000014841 denotes Shh
T12305 26766-26775 UBERON:0007376 denotes epidermis
T12306 26813-26820 UBERON:0000922 denotes embryos
T12307 26900-26905 NCBITaxon:10088 denotes mouse
T12308 26906-26920 UBERON:0002073 denotes hair follicles
T12309 27000-27007 UBERON:0000922 denotes embryos
T12310 27137-27140 PR:000014841 denotes Shh
T12311 27141-27151 GO:0010467 denotes expression
T12312 27196-27199 PR:000014841 denotes Shh
T12313 27308-27321 UBERON:0005086 denotes hair placodes
T12314 27335-27348 UBERON:0002073 denotes hair follicle
T12315 27335-27362 GO:0031069 denotes hair follicle morphogenesis
T12316 27407-27420 GO:0097617 denotes hybridization
T12317 27443-27450 UBERON:0000922 denotes embryos
T12318 27455-27464 PR:000002198 denotes β-catenin
T12319 27490-27500 GO:0010467 denotes expression
T12320 27512-27521 PR:000002198 denotes β-catenin
T12321 27525-27532 UBERON:0000922 denotes embryos
T12322 27589-27602 UBERON:0005086 denotes hair placodes
T12323 27617-27626 UBERON:0000922 denotes embryonic
T12324 27728-27741 UBERON:0005086 denotes hair placodes
T12325 27767-27776 UBERON:0000922 denotes embryonic
T12326 27805-27818 UBERON:0005086 denotes hair placodes
T12327 27868-27873 UBERON:0002101 denotes limbs
T12328 27933-27940 UBERON:0000922 denotes embryos
T12329 28007-28015 UBERON:0013623 denotes footpads
T12330 28023-28036 UBERON:0005086 denotes hair placodes
T12331 28122-28135 UBERON:0005086 denotes hair placodes
T12332 28157-28165 UBERON:0013623 denotes footpads
T12333 28199-28212 UBERON:0005086 denotes hair placodes
T12334 28235-28238 PR:000004122 denotes Apc
T12335 28239-28243 SO:0000704 denotes gene
T12336 29053-29062 UBERON:0000922 denotes embryonic
T12337 29053-29062 _FRAGMENT denotes embryonic
T12338 29077-29090 GO:0048598 denotes morphogenesis
T12339 29063-29076 UBERON:0002073 denotes hair follicle
T12340 29063-29090 GO:0031069 denotes hair follicle morphogenesis
T12341 29150-29163 UBERON:0002073 denotes hair follicle
T12342 29150-29177 GO:0031069 denotes hair follicle morphogenesis
T12343 29185-29190 GO:0007567 denotes natal
T14380 29216-29219 PR:000009454 denotes K14
T14381 29239-29242 PR:000004122 denotes Apc
T14382 29252-29261 UBERON:0007376 denotes Epidermal
T14383 29262-29272 UBERON:0004529 denotes Appendages
T14384 29299-29313 UBERON:0002073 denotes hair follicles
T14385 29315-29318 PR:000009454 denotes K14
T14386 29338-29341 PR:000004122 denotes Apc
T14387 29381-29390 UBERON:0007376 denotes epidermal
T14388 29391-29401 UBERON:0004529 denotes appendages
T14389 29417-29427 UBERON:0000483 denotes epithelial
T14390 29428-29439 UBERON:0003104 denotes mesenchymal
T14391 29505-29511 UBERON:0001091 denotes dental
T14392 29538-29543 UBERON:0001091 denotes Tooth
T14393 29617-29629 UBERON:0000924 denotes ectodermally
T14394 29638-29653 UBERON:0002424 denotes oral epithelium
T14395 29674-29713 UBERON:0007213 denotes cranial neural crest–derived mesenchyme
T14396 29728-29733 UBERON:0001091 denotes tooth
T14397 29760-29765 UBERON:0001091 denotes tooth
T14398 29826-29839 UBERON:0000167 denotes oral cavities
T14399 29875-29885 UBERON:0008281 denotes tooth buds
T14400 29919-29924 UBERON:0001091 denotes teeth
T14401 29945-29949 GO:0040007 denotes grow
T14402 29989-29993 UBERON:0001913 denotes milk
T14403 30003-30007 CHEBI:33290 denotes food
T14404 30026-30036 GO:0010467 denotes expression
T14405 30049-30052 PR:000009454 denotes K14
T14406 30057-30066 PR:000002198 denotes β-catenin
T14407 30095-30103 GO:0016020 denotes membrane
T14408 30110-30120 GO:0010467 denotes expression
T14409 30124-30133 PR:000002198 denotes β-catenin
T14410 30150-30153 PR:000009454 denotes K14
T14411 30154-30164 GO:0010467 denotes expressing
T14412 30165-30180 UBERON:0002424 denotes oral epithelium
T14413 30185-30196 CL:0000059 denotes ameloblasts
T14414 30207-30211 NCBITaxon:10088 denotes mice
T14415 30237-30240 PR:000009454 denotes K14
T14416 30241-30251 GO:0010467 denotes expressing
T14417 30277-30286 GO:0005829 denotes cytosolic
T14418 30287-30294 GO:0005634 denotes nuclear
T14419 30295-30304 PR:000002198 denotes β-catenin
T14420 30394-30404 UBERON:0008281 denotes tooth buds
T14421 30419-30423 NCBITaxon:10088 denotes mice
T14422 30462-30465 PR:000014841 denotes Shh
T14423 30466-30476 GO:0010467 denotes expression
T14424 30493-30506 UBERON:0007115 denotes primary teeth
T14425 30533-30536 PR:000004122 denotes Apc
T14426 30566-30584 UBERON:0006914 denotes squamous epithelia
T14427 30575-30594 UBERON:0001772 denotes epithelia of cornea
T14428 30575-30587 _FRAGMENT denotes epithelia of
T14429 30602-30610 _FRAGMENT denotes salivary
T14430 30626-30632 UBERON:0004809 denotes glands
T14431 30616-30632 UBERON:0004694 denotes Hardarian glands
T14432 30596-30600 _FRAGMENT denotes oral
T14433 30626-30632 UBERON:0010047 denotes glands
T14434 30676-30689 UBERON:0002073 denotes hair follicle
T14435 30715-30728 UBERON:0002073 denotes hair follicle
T14436 30715-30742 GO:0031069 denotes hair follicle morphogenesis
T14437 30770-30779 UBERON:0000483 denotes epithelia
T16819 30782-30785 PR:000009454 denotes K14
T16820 30797-30800 PR:000004122 denotes Apc
T16821 30830-30836 UBERON:0002370 denotes thymic
T16822 30837-30841 NCBITaxon:10088 denotes Mice
T16823 30842-30848 UBERON:0002370 denotes Thymus
T16824 30855-30860 UBERON:0000062 denotes organ
T16825 30888-30891 PR:000009454 denotes K14
T16826 30892-30902 GO:0010467 denotes expression
T16827 30944-30949 UBERON:0000062 denotes organ
T16828 30954-30963 CL:0000893 denotes thymocyte
T16829 31014-31028 CL:0002364 denotes TECs of cortex
T16830 31014-31021 _FRAGMENT denotes TECs of
T16831 31033-31040 CL:0002365 denotes medulla
T16832 31022-31028 UBERON:0001851 denotes cortex
T16833 31033-31040 UBERON:0000958 denotes medulla
T16834 31084-31092 UBERON:0001851 denotes Cortical
T16835 31084-31092 _FRAGMENT denotes Cortical
T16836 31107-31110 CL:0002364 denotes TEC
T16837 31097-31106 UBERON:0000958 denotes medullary
T16838 31097-31110 CL:0002365 denotes medullary TEC
T16839 31153-31163 GO:0010467 denotes expression
T16840 31189-31191 PR:000009495 denotes K8
T16841 31193-31196 PR:000009458 denotes K18
T16842 31198-31200 PR:000009481 denotes K5
T16843 31206-31209 PR:000009454 denotes K14
T16844 31222-31228 UBERON:0002370 denotes thymus
T16845 31253-31258 UBERON:0000062 denotes organ
T16846 31265-31271 UBERON:0009911 denotes lobule
T16847 31305-31308 CL:0002293 denotes TEC
T16848 31332-31338 UBERON:0001851 denotes cortex
T16849 31352-31359 UBERON:0000958 denotes medulla
T16850 31424-31430 UBERON:0002370 denotes thymus
T16851 31512-31513 CHEBI:51686 denotes H
T16852 31528-31534 UBERON:0002370 denotes thymus
T16853 31540-31546 UBERON:0001851 denotes cortex
T16854 31567-31582 UBERON:0001744 denotes lymphoid tissue
T16855 31625-31631 UBERON:0003891 denotes stroma
T16856 31639-31646 UBERON:0000958 denotes medulla
T16857 31680-31691 CL:0000542 denotes lymphocytes
T16858 31701-31707 UBERON:0001851 denotes cortex
T16859 31713-31720 UBERON:0000958 denotes medulla
T16860 31751-31757 UBERON:0001851 denotes cortex
T16861 31769-31773 NCBITaxon:10088 denotes mice
T16862 31779-31785 UBERON:0002370 denotes thymus
T16863 31819-31824 UBERON:0007023 denotes adult
T16864 31833-31842 GO:0060033 denotes regresses
T16865 31886-31890 NCBITaxon:10088 denotes mice
T16866 31932-31942 CL:0000893 denotes thymocytes
T16867 31948-31959 GO:0007067 denotes mitotically
T16868 31974-31980 UBERON:0001851 denotes cortex
T16869 31998-32002 CHEBI:472552 denotes BrdU
T16870 32062-32068 UBERON:0002370 denotes thymus
T16871 32084-32088 NCBITaxon:10088 denotes mice
T16872 32127-32130 PR:000009454 denotes K14
T16873 32143-32153 GO:0010467 denotes expression
T16874 32194-32198 CL:0002293 denotes TECs
T16875 32212-32221 UBERON:0000958 denotes medullary
T16876 32240-32253 CL:0000312 denotes keratinocytes
T16877 32257-32277 UBERON:0003987 denotes Hassall's corpuscles
T16878 32299-32310 GO:0005737 denotes cytoplasmic
T16879 32324-32333 PR:000002198 denotes β-catenin
T16880 32359-32368 UBERON:0000958 denotes medullary
T16881 32369-32379 UBERON:0000483 denotes epithelial
T16882 32369-32385 CL:0000066 denotes epithelial cells
T16883 32414-32417 PR:000009454 denotes K14
T16884 32418-32428 GO:0010467 denotes expression
T16885 32451-32453 PR:000009495 denotes K8
T16886 32470-32480 UBERON:0000483 denotes epithelial
T16887 32470-32486 CL:0000066 denotes epithelial cells
T16888 32499-32506 UBERON:0000958 denotes medulla
T16889 32511-32517 UBERON:0001851 denotes cortex
T16890 32531-32533 PR:000009450 denotes K1
T16891 32569-32573 NCBITaxon:10088 denotes mice
T16892 32593-32597 NCBITaxon:10088 denotes mice
T16893 32632-32645 CL:0000312 denotes keratinocytes
T16894 32657-32677 UBERON:0003987 denotes Hassall's corpuscles
T16895 33241-33247 UBERON:0002370 denotes thymus
T16896 33314-33320 UBERON:0002370 denotes thymus
T16897 33337-33344 UBERON:0009911 denotes lobules
T16898 33362-33366 NCBITaxon:10088 denotes mice
T16899 33382-33388 UBERON:0002370 denotes thymus
T16900 33626-33632 UBERON:0002370 denotes thymus
T16901 33768-33774 UBERON:0002370 denotes thymus
T16902 33896-33902 UBERON:0002370 denotes thymus
T16903 34001-34011 UBERON:0000483 denotes epithelial
T16904 34028-34034 UBERON:0002370 denotes thymus
T16905 34099-34109 CL:0000893 denotes thymocytes
T16906 34125-34131 UBERON:0001851 denotes cortex
T16907 34199-34200 CHEBI:51686 denotes H
T16908 34240-34246 UBERON:0001851 denotes cortex
T16909 34261-34268 UBERON:0000958 denotes medulla
T16910 34313-34320 GO:0005634 denotes nuclear
T16911 34321-34330 PR:000002198 denotes β-catenin
T16912 34364-34373 UBERON:0000958 denotes medullary
T16913 34395-34404 PR:000002198 denotes β-catenin
T16914 34482-34485 PR:000009454 denotes K14
T16915 34520-34527 UBERON:0000958 denotes medulla
T16916 34553-34555 PR:000009495 denotes K8
T16917 34605-34611 UBERON:0002370 denotes thymus
T16918 34625-34642 UBERON:0003846 denotes thymic epithelial
T16919 34698-34709 CL:0000542 denotes lymphocytes
T16920 34826-34836 CL:0000893 denotes thymocytes
T16921 34869-34875 UBERON:0002370 denotes thymus
T16922 34885-34895 UBERON:0000483 denotes epithelial
T16923 34885-34901 CL:0000066 denotes epithelial cells
T16924 34994-34999 UBERON:0002370 denotes thymi
T16925 35022-35028 UBERON:0002370 denotes thymus
T16926 35046-35049 PR:000009454 denotes K14
T16927 35050-35060 GO:0010467 denotes expression
T16928 35082-35084 PR:000009495 denotes K8
T16929 35085-35095 GO:0010467 denotes expression
T16930 35136-35147 CL:0000646 denotes basal cells
T16931 35165-35169 CL:0002293 denotes TECs
T16932 35248-35255 GO:0005634 denotes nuclear
T16933 35260-35271 GO:0005737 denotes cytoplasmic
T16934 35272-35281 PR:000002198 denotes β-catenin
T16935 35308-35315 GO:0005634 denotes nuclear
T16936 35328-35337 PR:000002198 denotes β-catenin
T16937 35381-35387 UBERON:0002370 denotes thymus
T16938 35419-35422 PR:000009454 denotes K14
T16939 35427-35436 PR:000002198 denotes β-catenin
T16940 35522-35528 UBERON:0002370 denotes thymus
T16941 35560-35579 UBERON:0003987 denotes Hassall's corpuscle
T16942 35615-35618 PR:000009454 denotes K14
T16943 35624-35626 PR:000009495 denotes K8
T16944 35627-35637 GO:0010467 denotes expressing
T16945 35638-35650 GO:0031424 denotes keratinizing
T16946 35638-35650 _FRAGMENT denotes keratinizing
T16947 35662-35667 CL:0000311 denotes cells
T16948 35651-35661 UBERON:0000483 denotes epithelial
T16949 35651-35667 CL:0000066 denotes epithelial cells
T16950 35743-35754 CL:0000775 denotes neutrophils
T16951 35759-35770 CL:0000235 denotes macrophages
T16952 35788-35794 UBERON:0002370 denotes thymus
T16953 35956-35960 NCBITaxon:10088 denotes mice
T16954 35975-35977 PR:000009450 denotes K1
T16955 35982-35992 PR:000009167 denotes involucrin
T16956 36027-36047 UBERON:0003987 denotes Hassall's corpuscles
T16957 36078-36083 UBERON:0002370 denotes thymi
T16958 36106-36110 NCBITaxon:10088 denotes mice
T16959 36114-36124 CL:0000893 denotes thymocytes
T16960 36142-36146 CHEBI:472552 denotes BrdU
T16961 36191-36203 GO:0031424 denotes keratinizing
T16962 36191-36203 _FRAGMENT denotes keratinizing
T16963 36215-36220 CL:0000311 denotes cells
T16964 36204-36214 UBERON:0000483 denotes epithelial
T16965 36204-36220 CL:0000066 denotes epithelial cells
T16966 36302-36312 GO:0010467 denotes expression
T16967 36316-36325 PR:000002198 denotes β-catenin
T16968 36352-36362 UBERON:0000483 denotes epithelial
T16969 36352-36368 CL:0000066 denotes epithelial cells
T16970 36416-36423 GO:0005634 denotes nuclear
T16971 36424-36433 PR:000002198 denotes β-catenin
T16972 36481-36485 NCBITaxon:10088 denotes mice
T16973 36496-36503 GO:0005634 denotes nuclear
T16974 36520-36529 PR:000002198 denotes β-catenin
T16975 36551-36554 PR:000009454 denotes K14
T16976 36604-36615 CL:0000646 denotes basal cells
T16977 36630-36634 NCBITaxon:10088 denotes mice
T16978 36667-36677 GO:0010467 denotes expression
T16979 36700-36706 UBERON:0002370 denotes thymus
T16980 36759-36768 PR:000002198 denotes β-catenin
T16981 36769-36779 GO:0010467 denotes expression
T16982 36840-36842 PR:000009495 denotes K8
T16983 36843-36846 PR:000009454 denotes K14
T16984 36847-36857 GO:0010467 denotes expression
T16985 36937-36943 UBERON:0002370 denotes thymus
T16986 36994-36997 PR:000004122 denotes Apc
T16987 37030-37039 PR:000002198 denotes β-catenin
T16988 37043-37046 PR:000009454 denotes K14
T16989 37047-37057 GO:0010467 denotes expressing
T16990 37058-37062 CL:0002293 denotes TECs
T16991 37086-37099 GO:0008283 denotes proliferation
T16992 37104-37136 GO:0030216 denotes differentiation to keratinocytes
T16993 37123-37136 CL:0000312 denotes keratinocytes
T16994 37202-37211 UBERON:0000958 denotes medullary
T16995 37202-37211 _FRAGMENT denotes medullary
T16996 37224-37228 CL:0002365 denotes TECs
T16997 37215-37223 UBERON:0001851 denotes cortical
T16998 37215-37228 CL:0002364 denotes cortical TECs
T16999 37245-37248 CL:0002293 denotes TEC
T17000 37295-37305 CL:0000893 denotes thymocytes
T17001 37329-37333 NCBITaxon:10088 denotes mice
T17002 37342-37348 UBERON:0002370 denotes thymic
T18947 0-37367 PR:000004122 denotes Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus Role of APC in Skin and Its Appendages Abstract The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre–mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; ApcCKO/CKO mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial–mesenchymal interactions for their development. Synopsis Patients with familial adenomatous polyposis (FAP) and its variant, Gardner's syndrome, will develop hundreds of colorectal polyps. It is a heritable disease that is linked to a genetic mutation in the tumor suppressor gene APC (adenomatous polyposis coli). These individuals also develop extracolonic symptoms, among which are congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, epidermoid cysts, disorders of the maxillary and skeletal bones, and dental abnormalities, suggesting the importance of APC functions in these organs. To understand the role of Apc in development and in organs other than intestine, we generated Apc mutant mice that can conditionally delete the gene when exposed to Cre recombinase. These mice were mated with K14 (Keratin 14)–cre mice that express Cre recombinase in skin and its appendages. The authors found that the mutant mice that have lost Apc in K14-cre transgene–expressing tissues were viable, but had stunted growth and died before weaning. These mutant mice showed developmental abnormalities not only in skin but also in many epithelial-derived tissues, including teeth and thymus. This work demonstrates the importance of Apc in development of many organs, and provides new insights into diagnosis and management of patients with APC mutations. Introduction Adenomatous polyposis coli (APC) is a member of the Wnt signaling pathway and one of its known functions is to regulate the levels of β-catenin. Alterations in β-catenin regulation are very common in human tumors [1]. Loss of APC is associated with stabilization of the cytosolic β-catenin that ultimately results in its migration to the nucleus and activating a cascade of events leading to tumorigenesis. APC also interacts with a multitude of other cellular proteins, including axin-2 (AXIN2), plakoglobin (JUP), Asef (ARHGEF4), kinesin superfamily–associated protein 3 (KIFAP3), EB1 (MAPRE1), microtubules, and the human homolog of Drosophila discs large (DLG1). These interactions suggest that APC can potentially regulate many cellular functions, including intercellular adhesion, cytoskeletal organization, regulation of plakoglobin levels, regulation of the cell cycle and apoptosis, orientation of asymmetric stem cell division, and control of cell polarization [2,3]. APC is a tumor suppressor gene. Somatic mutations in APC are frequently found in many sporadic tumors of the colon and rectum. Autosomal dominant germline mutations in APC cause familial adenomatous polypois (FAP) and its variant, Gardner syndrome. FAP patients are characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer in the third and fourth decades of life [4,5]. In addition to colorectal neoplams, these individuals can develop extracolonic symptoms, among which are upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, disorders of the maxillary and skeletal bones, and dental abnormalities [6], suggesting the importance of APC gene functions in these organ systems. Although the role of APC in the initiation of human colorectal cancer is well established, its role in other tissue and developmental processes are not well understood. Given the importance of regulation of Wnt signaling in embryonic pattern formation and morphogenesis of many organs, mechanistic understanding of APC in development and in extracolonic tissues becomes critical to better assess potential adverse events in humans. One approach to understand the role of Apc in development is to develop mice with an inactivating Apc mutation. Several genetically modified mouse strains for Apc have been described [7–10]. Most of these models, in the heterozygous state, show a gastrointestinal and other tumor predisposition phenotype [7–10]. Mouse embryos that are homozygous for the genetic modification die during embryogenesis, and some of the models do not survive beyond gastrulation [8,11]. An alternate approach to understand the role of Apc in development and/or in specific tissues is to generate a mouse strain that carries a conditionally modified allele and mate it with a mouse strain that facilitates the modification of the conditional allele in specific cell lineages. To assess the role of Apc in different stages of life systematically, we generated mice containing a conditional knockout (CKO) mutant allele of Apc (ApcCKO). These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. We report here that K14 promoter-driven loss of Apc resulted in aberrant development of several organs that require inductive epithelial–mesenchymal interactions, including hair follicle, teeth, and thymus, and resulted in neonatal death in mice. We found that Apc plays a crucial role in determinations of cell fates during the embryonic development, possibly via temporal and tissue-specific regulation of β-catenin levels in the skin, its appendages, and in the thymus. Results Generation of the ApcCKO and ApcΔ580 Mice To investigate the role of Apc in development of skin and its appendages, we used the Cre/loxP technology to introduce a conditional mutation of the Apc gene in mice. We constructed embryonic stem (ES) cells and mice carrying an Apc allele harboring both a pair of loxP sites flanking Apc exon 14 and a pair of FLP recognition target (FRT) sites flanking PGK-neomycin selection cassette by recombineering [12,13] (Figure 1A, ApcCKON allele, N for neomycin cassette). A PGK-neomycin cassette was inserted in the same transcriptional orientation as Apc in intron 14 of the endogenous gene. The loxP and FRT sites were used to aid unidirectional recombination [12,13]. Two mouse lines containing the same modification were generated from two independent ES clones to ensure that these two lines behave in the same way. These ApcCKON/+ mice were crossed with FLPe-deleter to generate ApcCKO/+ mice that were heterozygous for the final Apc conditional (ApcCKO) allele that removed the PGK-neomycin cassette and contains only the loxP sites in the introns flanking exon 14. To assess the effect of deleting exon 14 in mice, both lines of ApcCKO/+ mice were crossed with the Cre-deleter to generate the germline knockout line of Apc, designated ApcΔ580/+. The mutant allele (ApcΔ580) lacks exon 14 (Figure 1A). The transcript from loss of exon 14 results in a shift in the normal reading frame, resulting in a premature chain termination codon which, if utilized, would result in a truncated polypeptide that is 605 aa in length, of which the first 580 aa correspond to the normal Apc protein. Figure 1 Generation of the Conditional Apc Allele (A) Schematic diagram of exons 14 and 15 of the mouse Apc gene, the targeting vector, and the resulting conditional allele with 2 LoxP sites sandwiching the exon 14. The PGK-neomycin cassette was inserted within intron 14 by recombineering technique. This cassette is sandwiched by 2 FRT sites that could be removed by crossing to FLPe-expressing mice. Positions of PCR primers used for genotyping PCR (F2, R2, R4) and RT-PCR (F546 and R721) are indicated. Positions of probe used for Southern blot analysis with NdeI sites are also shown. Upon Cre-mediated recombination, exon 14 is removed and leads to truncated Apc protein, of which the first 580 aa correspond to the normal. (B) Southern blot analysis of NdeI-digested genomic tail DNA isolated from F1 mice of various Apc mouse lines (ApcCKON, ApcΔ580), hybridized to a 600-bp probe. Tail genomic DNA from ApcCKON F1 mice derived from a modified ES clone showed a 12-kb band for the ApcCKON allele and a 10-kb band for the wild-type allele, whereas genomic DNA from the ApcΔ580 mouse was heterozygous for the ApcΔ580 allele (9.2-kb band). (C) Kaplan-Meier survival plot of ApcCKO/+ mice (thin solid line, n = 39), ApcCKO/CKO mice (thin dotted line, n = 57), ApcΔ580/+ mice (solid line, n = 51), and wild-type littermates (broken line, n = 21). Heterozygosity of the ApcΔ580 allele led to a significantly shortened survival (p < 0.0001), whereas those of heterozygous and homozygous ApcCKO mice had no significant difference to that of wild-type littermates. Southern blot analysis of tail DNA from F1 offspring of both ApcCKON and ApcΔ580 lines confirmed the germline transmission of modified Apc allele (Figure 1B). Mice that are heterozygous for ApcΔ580 mutation are viable but have a significantly reduced lifespan (Figure 1C). These results suggested that deletion of exon 14 indeed results in either loss or abnormal function of the Apc gene product. ApcΔ580/+ mice have median survival of 5 mo of age (Figure 1C), with progressive signs of rectal bleeding and anemia. Similar to the results reported with an independently generated ApcΔ580/+ conditional mouse strain [14], ApcΔ580/+ mice had more than 100 (120 ± 37, n = 11) intestinal tumors at the time of their death (Figure S1). Inactivation of wild-type Apc is an important prerequisite for tumor development. We analyzed 30 intestinal tumors from ApcΔ580/+ mice by in vitro transcription and translation assay, but none of them showed truncated Apc products (unpublished data), indicating that the most likely mechanism of wild-type Apc inactivation is by allelic loss. The mutant allele had to be maintained and transmitted through male mice, as ApcΔ580/+ females were frequently not healthy enough to successfully nurse their own pups because of their tumor burden. ApcCKO/+ mice were intercrossed to generate ApcCKO/CKO offspring. Approximately one-quarter of the offspring (17 of 81) were homozygous for the ApcCKO allele. These mice as well as heterozygous mice for ApcCKO allele are normal, showing no differences in their survival to the wild-type littermates (Figure 1C). We tested whether our ApcCKO allele can compliment the wild-type allele by crossing the ApcCKO/CKO female with ApcΔ580/+ male mouse. The resultant ApcCKO/Δ580 offspring were viable and born in the Mendelian ratio, suggesting that the presence of loxP sites in introns flanking exon 14 have no adverse effect on the function of the Apc gene. K14-Driven Loss of Apc Results in Severe Growth Retardation and Early Lethality To introduce the mutation of Apc into cells expressing K14, we crossed WW6 ES cell–derived [15] ApcCKO/+ mice with K14-cre recombinase mice in FVB background [16]. The K14-cre; ApcCKO/+ mice were normal in appearance and were fertile. K14-cre; ApcCKO/+ males were crossed to ApcCKO/CKO females to avoid the potential deleter effect in oocytes of K14-cre–positive females [17]. The mice were intercrossed thereafter for maintenance; hence, the mice used for analysis were in a mixed background of FVB, 129/S, and C57BL/6 in similar proportions, with minimal contribution of SJ. The K14 promoter is a commonly used epidermal cell promoter because of its expression by the mitotically active cells of the epidermis and its appendages in mature skin [18], but most notably it is active in embryonic ectoderm as early as the single layered ectodermal stage of embryonic day (E) 9.5 [19]. A restricted expression of K14 is also found in thymic epithelial cells (TECs) in the medulla of normal thymus [20]. We genotyped a total of 458 pups (8–10 d old) from 67 litters resulting from crosses between K14-cre; ApcCKO/+ and ApcCKO/CKO mice. The mutant mice of the genotype K14-cre; ApcCKO/CKO (hereafter, KA mutant) were born, but the observed frequency of KA mutants was much less than expected (78 of 458 [17.0%]; p < 0.0005 Chi-square analysis, Table 1). To assess the basis for the neonatal lethality of KA mutants, we monitored three litters from birth to weaning by measuring the body weight of each pup every day. A total of 25 pups were born from three litters, of which 7 (28%) were confirmed to be K14-cre; ApcCKO/CKO by genotyping, indicating that KA mutants were born in the expected Mendelian ratio. The KA mutant pups were nursed normally, and there was milk in their stomachs during the first 2 or 3 d after birth, but they failed to thrive (Figure 2). By postnatal day (P) 8–10, at the time of genotyping, many KA mutant pups were considerably smaller than their littermates (Figure 2B–2F) and some have died at or prior to this age. None of KA mutants survived to weaning age. Table 1 Genotype Distribution of Progeny from the Matings Figure 2 Postnatal Mortality and Stunted Growth in K14-cre; ApcCKO/CKO Mutant Mice Animals whose genotype is either heterozygous or homozygous for the wild-type Apc allele are referred to as normal (N); those whose genotype are K14-cre; ApcCKO/CKO and show the presence of K14-cre–recombined mutant Apc allele are called mutant (M). (A) Two P3 mutant mice, M1 and M2, and their normal littermates, showing size variation among mutants. (B) P8 mutant mouse (right) and a normal littermate. Note sparseness of hair coat and abnormal ears. (C–D) Vibrissae of whisker pads are short and oddly angled in a P12 mutant mouse (C), relative to control (D). Note the lack of incisors in the mutant. (E) A P17 mutant mouse (right) with its littermate. Its bare forehead, dorsal median line, and abnormal ears are evident. (F) Growth curve of mutants and normal littermates. Mutants exhibit stunted growth, which became more prominent as they aged, and weigh significantly less than littermates from P8 (p < 0.05). (G) Comparison of mutant and normal thymus from P3 mice. The mutant thymus (left) is dramatically smaller for its age compared to the normal littermate (right). The scale bar equals 1 mm. (H) Skeletal preparations of normal (left) and mutant (right), showing differences in development of both incisor (I) and molar (M) teeth. The ability of whole embryos to exclude blue dye was used to examine the epidermal barrier, normally acquired beginning at E16 and complete by E18.5 [21]. Analyses of E17.5–E18.5 KA mutants showed that they were able to exclude blue dye, indicating that the epidermal barrier was intact (Figure S2). At these embryonic ages, there were no differences in size between the mutants and their littermates, but the mutants showed a patch of “birthmark” or dark pigmentation on their foreheads and a dark median line that ran caudally from head to tail. Their external ears or pinnae were shriveled in appearance and pigmented compared to those of littermates. External characteristics of KA mutants that were evident at E18.5 persisted after birth and became more prominent as they grew (Figure 2A–2F). Growth of pelage hair was generally delayed in the mutants. At around P8, the KA mutants were hairless and had wrinkled skin while their phenotypically normal littermates had a smooth thin coat of hair (Figure 2B). At this age, two lower incisors start to erupt in normal littermates and these were absent in the KA mutants (Figure 2C and 2D). Animals also tended to be smaller and around P10–P12 displayed abnormally short and misshapen vibrissae and short, shaggy pelage hairs (Figure 2C and 2D). Development of thick ridges in their skin, particularly around the ears, eyelids, forehead, nose, and paws, became noticeable (Figure 2E). These regions looked scaly, and these animals hardly kept their eyes open. In contrast to the normal littermates that consistently increased their body weight with age, surviving KA mutants started to lose weight from P10 onwards; by P16–P17 they were all lethargic, and none of them survived to weaning (Figure 2E and 2F). At the time of autopsy all the mutants were toothless, without incisors or molars, and their stomachs were consistently small and had no solid food, unlike their age-matched littermates, suggesting that the observed weight loss could be the result of failure to ingest solid food (Figure 2F). Interestingly, changes in body weights and timing of hair growth varied considerably among mutant pups even if they were from the same litter, whereas those of phenotypically normal littermates tended to be similar. This difference was also reflected in the variation in timing of death in mutants: some mutant pups were born alive but died within a day or two, some survived close to the weaning age. This variability of the mutant phenotypes suggests possible variation in the timing and efficiency of cre-mediated Apc deletion. It is possible that the genetic background has a role to play in this variability. Gross examination of internal organs also showed that the mutants' thymi were consistently inconspicuous and were very small for their age, whereas those of their littermates were very prominent in size (Figure 2G). This difference was evident as early as P3. Quite frequently mutant thymi in P12–P17 mutant mice also contained black deposits within the tissue (unpublished data). Mutant mice were also examined for any skeletal abnormalities by preparing skeletal specimens of P16–P17 mice stained with Alizarin red. No differences between the normal and KA mutant mice in the mandibular bone can be detected, but the mutant mice lacked or had underdeveloped set of maxillary incisors and molars (Figure 2H). We detected no other major skeletal abnormalities. Genotype- and Tissue-Specific Expression of the Truncated Apc Transcripts To assess the molecular effects of the K14-cre–mediated recombination, we screened for the presence of deleted Apc (ApcΔ580) alleles. Genomic DNA was extracted from liver, thymus, and skin from all 4 possible genotypes: K14-cre; ApcCKO/CKO, K14-cre; ApcCKO/+, ApcCKO/CKO, and ApcCKO/+. Genotyping on genomic DNA from these tissues showed that the ApcΔ580 allele (500-bp product) was detected only from the skin and thymus of the K14-cre–positive mice. The presence of mutant Apc allele in the thymus of K14-cre; ApcCKO/+ mice was consistently much less than the DNA from the skin of the same animal or other tissues from the KA mutants. In addition, this product was not detected at all in either the liver of K14-cre–positive or in any of the K14-cre–negative mouse tissues samples, establishing that Cre-mediated recombination has taken place in the tissue-specific manner in the mice that inherited K14-cre (Figure 3A). Figure 3 Tissue-Specific Detection and Expression of Deleted Apc Alleles (A) Tissue-specific genotyping PCR. Only genomic DNA samples from the skin (S) and thymus (T), but not liver (L) of mice positive for K14-cre show the presence of deleted ApcΔ580 allele. (B) Genotype- and tissue-specific expression of the truncated Apc transcripts. A representative gel of RT-PCR using primers F546 and R721, showing that only RNA from the skin and thymus but not liver of mice positive for K14-cre have transcripts from both wild-type (528 bp) and deleted (313 bp) Apc alleles. Apc transcripts were also analyzed by RT-PCR with primers spanning exon 14 (Figure 1A) using total RNA isolated from the corresponding tissue samples. We detected the expected RT-PCR product (313 bp) from the truncated Apc (ApcΔ580) allele only in the tissues where Cre recombinase is known to be expressed in the K14-cre–positive mice. However, this product was not detected in either the K14-cre–negative mouse tissues samples or the liver of K14-cre–positive mice, and only the product from the wild-type allele (528 bp) was detected from these RNA samples, further confirming that Cre-mediated recombination has taken place in the tissue- and genotype-specific manner (Figure 3B). K14-cre–Driven Apc Loss Induced Aberrant Hair Follicles throughout the Epidermis To understand the basis for delayed and abnormal hair development in the KA mutants, we conducted a histological and immunohistochemical examination (Figure 4). The hair follicle is an epidermal appendage that consists of an upper permanent portion, and a lower cycling portion that produces the hair [22,23]. The outer root sheath (ORS) is contiguous with and biochemically similar to the basal layer of the epidermis. The inner layers of the hair follicle include three concentric layers of inner root sheath and three concentric layers of hair-producing cells. At the base of the hair follicle is the germinative hair follicle bulb, which contains rapidly proliferating “matrix” cells that differentiate to populate all of the layers of the inner root sheath and the hair shaft itself [22]. During the anagen phase of the hair cycle (until P15), hair follicles of phenotypically normal mice grew deeply into the subcutaneous fat and were uniformly spaced and aligned in parallel arrays at a specific angle relative to the skin surface (Figure 4A). In contrast, KA mutant follicles were irregularly spaced and often seen as disoriented and clamped invaginations at P3 that became even more remarkable at P12 when the mutant mice were covered by fur coat (Figure 4F). Bulbs were often bent in addition to being irregularly angled to one another and their sizes and locations were often variable. Clusters of multiple invaginations or dysplastic follicular structures were frequently observed throughout the epidermis, whereas other regions showed gaps with no follicles. Serial sectioning indicated that some of the hair follicles in the P12 mutant skin were not properly formed or shorter than normal. Taken together, these features could account for the apparently delayed, followed by outgrowth, of the short and shaggy-looking fur coat of these mutant mice. Figure 4 Histological and Immunochemical Examination of P12 Skin and Teeth (A–E) P12 normal skin. (F–J) P12 mutant skin. (K–N) P12 normal oral cavity. (O–R) P12 mutant oral cavity. Stained with H&E for histology (A, F, K–L, O–P), Ki67 (B, G), β-catenin (C, H, M, Q), K14 (D, I, N, R), and K6 (E, J). Aberrant follicular morphogenesis, characterized by formation of irregularly spaced, nonpolarized hair follicles, in mutant skin is evident. Despite the abnormal histology, proliferation seems to be confined to hair bulb-like structures (arrows in [G], inset [G′] at higher magnification), but in mutant skin (arrows in [H], inset [H′] at higher magnification) and oral cavity (arrows in insets [Q′] at higher magnification) elevated cytosolic localization of β-catenin is detected in some cells. Scale bars: 50 μm for (A–F), (H–J); 250 μm for (K) and (O); 100 μm for (G), (L–N), (P–R); 20 μm for (Q′). Apc is a regulator of β-catenin that is important for Wnt signaling. We examined the patterns of expression of β-catenin in the affected tissues. In the normal skin, β-catenin, a member of the adherens junction complex, was found in the ORS of hair follicles and basal layer of epidermis, where K14 expression is also observed (Figure 4C and 4D), whereas the expression of K1, involucrin, and loricrin (markers for spinous and granular layers of epidermis) was only observed in the nonbasal epidermis (unpublished data). The patterns of expression of K14, K1, involucrin, and loricrin, in skin from mutant and normal littermate mice at P3–P17, showed no significant differences in the terminal differentiation (Figure 4A–4D, 4F–4I). Similarly, the pattern of expression of K6, which is normally only expressed in the suprabasal or inner layer of the ORS of the hair follicle but not in the epidermis (Figure 4E), did not change. Due to the abnormal and disorganized structure of hair follicles themselves, K6 localization highlighted the histological abnormality (Figure 4J). Yet as in the normal skin, K6 was principally seen only in the suprabasal layer of the ORS that did not colocalize with the basal markers, K14 or K5 (Figure 4I and 4J). In normal skin, proliferating cells were detected in either the basal layer of epidermis or in germinative hair follicle bulbs at the base (Figure 4B). In the mutant skin, either BrdU incorporation or Ki67 expression was observed not only in cells in bulbs at the base of the hair follicle but also in bulb-like structures that were budding out from the ORS of the existing hair follicles (Figure 4G and 4G′). Each budding tip was becoming like a hair follicle bulb containing proliferating cells. Hence, despite the abnormal histology in the mutant skin, proliferation seems to be confined to bulb-like structures as in the normal skin (Figure 4G and 4G′). The exact locations of hair follicle bulbs were not as easy to define for some mutant follicles due to their disorganized structures. Interestingly, in the mutant skin, in addition to diffuse membrane-bound localization as in the normal skin, cells with strong cytosolic β-catenin localization were also observed frequently (Figure 4H and 4H′). These elevated β-catenin–expressing cells were usually surrounded by proliferating cells, forming bulb-like structures. Comparison of immunochemically stained serial sections showed that these intense cytosolic β-catenin stainings were usually found in either K14-positive K1-negative basal epidermis or K14-positive K6-negative basal ORS cells, and are surrounded by proliferating cells. To determine the initiation of hair follicle morphogenesis in these mutants, we examined the expression pattern of Sonic hedgehog (Shh), a factor expressed in hair bulbs in embryonic skin (Figure 5). The aberrant hair follicle morphogenesis is evident as early as E14.5 in mutant embryonic skin, by multiple apolarized expression of Shh throughout the epidermis (Figure 5B), whereas that of control embryos was well polarized and regularly spaced (Figure 5A). With development, control mouse hair follicles invaginate downward in a polarized manner (Figure 5C), whereas those of mutant embryos were completely irregular and apolarized (Figure 5D). It was also noted that the size of each “budding” follicle, as detected by Shh expression, was variable (Figure 5D). The intensity of Shh staining was generally stronger in mutant skin than in the normal skin. The aberrant initiation of multiple hair placodes during early hair follicle morphogenesis was also evident by the whole-mount in situ hybridization (ISH) of E15.5 mutant embryos for β-catenin (Figure 5F and 5F′). The expression pattern of β-catenin in embryos clearly demonstrated the formation of regular arrays of hair placodes in the normal embryonic skin (Figure 5E and 5E′), but such regular patterning was lost, and often tightly clustered abnormal hair placodes were initiated in mutant embryonic skin (Figure 5F′). Aberrant hair placodes were also evident throughout the skin surface of limbs in E15.5 mutants (Figure 5F), whereas those of the control embryos had not yet formed (Figure 5E). Most interestingly, in the mutant footpads, where hair placodes do not normally form (Figure 5G), we also found ectopic irregularly sized and spaced hair placodes, indicating that the footpads still have the potential to form hair placodes in the absence of the Apc gene (Figure 5H). Figure 5 Expression of Shh and β-catenin Transcripts in Normal (ApcCKO/CKO) and Mutant (K14-cre; ApcCKO/CKO) Embryonic Skin (A–D) Section ISH with Shh probe in E14.5 normal (A), E14.5 mutant (B), E16.5 normal (C), and E16.5 mutant (D) skin. Broken lines indicate the interface between epithelium and mesenchyme. Scale bars: 50 μm. Whole mount in situ detection of β-catenin in E15.5 normal (E, G), mutant (F, H) embryos. Aberrant initiation of multiple hair placodes is evident at E14.5. Loss of K14-driven Apc loss caused aberrant pattern formation (F′) and formed ectopic hair placodes in normally hairless foot pads (H, arrows) which are absent in normal (G). These results collectively suggest that the terminal differentiation does take place normally in the mutant skin, but initiation of embryonic hair follicle morphogenesis is severely disrupted, accompanied by a continuous ectopic hair follicle morphogenesis in postnatal mutant skin. Effects of K14-cre–Driven Loss of Apc in Other Epidermal Appendages Similar to the biology of hair follicles, K14-cre–driven loss of Apc also affected the development of other epidermal appendages that depend on epithelial–mesenchymal interactions for their formation. The most striking of these was dental dysplasia (Figure 4K–4R). Tooth development is normally initiated between E11 and E12 by invagination of ectodermally derived oral epithelium into the underlying cranial neural crest–derived mesenchyme, generating a tooth germ. Despite the grossly toothless phenotype of KA mutants, histological analysis of their oral cavities revealed the formation of multiple tooth buds at each location. These aberrant teeth obviously failed to grow out during the dietary transition from milk to solid food. Analogous to the expression patterns of K14 and β-catenin in the normal skin, diffuse membrane-bound expression of β-catenin was detected in K14-expressing oral epithelium and ameloblasts of normal mice. In mutants, some of the K14-expressing cells also showed strong cytosolic/nuclear β-catenin staining, as observed in the mutant skin (Figure 4Q, 4Q′, and 4R). Initiation of ectopic tooth buds in the mutant mice was evident at E15.5 by extra dots of Shh expression adjacent to the primary teeth (data not shown). Loss of Apc also leads to hyperplasia in squamous epithelia of cornea, oral, salivary, and Hardarian glands (unpublished data). Squamous metaplasia to hair follicle–like structures, ectopic hair follicle morphogenesis was also observed in these epithelia. K14-cre–Driven Apc Loss Results in Hypoplastic/Athymic Mice Thymus is an organ that is also known to have K14 expression [16]. It represents the primary lymphoid organ for thymocyte development and selection. Distinct population of TECs of cortex and medulla mediates both of these critical functions. Cortical and medullary TEC subsets are characterized by differential expression of four keratin species: K8, K18, K5, and K14. The normal thymus is a lobulated lymphoid organ, each lobule clearly showing the two distinct TEC compartments, an outer cortex and an inner medulla (Figure 6). There were no major differences in the histology of thymus between the ages P3 to P17 in phenotypically normal littermates. As shown in the H&E staining of thymus, the cortex was formed of dense lymphoid tissue that lacks nodules (Figure 6A). Since the stroma of the medulla is less heavily infiltrated with lymphocytes than the cortex, the medulla stained more lightly than the cortex. In normal mice, the thymus retains its size until the young adult age and regresses thereafter by atrophy. In the normal young mice we examined (P3–P17), it is evident that thymocytes were mitotically active in the cortex as determined by BrdU immunostaining (Figure 6B). Immunohistochemistry of normal thymus from P3 to P17 mice showed a similar staining pattern for K14 in that its expression was restricted to a small population of TECs in the inner medullary region and in the keratinocytes in Hassall's corpuscles (Figure 6D). Diffuse cytoplasmic staining for β-catenin was also detected in the medullary epithelial cells (Figure 6C). In contrast to K14 expression, diffuse staining for K8 was observed in epithelial cells both in the medulla and cortex (Figure S3). K1 staining was not detected in young mice at P3 but in older mice it was detected in differentiated keratinocytes in some of Hassall's corpuscles (Figure S3). Figure 6 Histological and Immunochemical Examination of Thymus (A–D) P3 normal thymus. (E–G) Mild P3 mutant thymus. (H–K) Severe P3 mutant thymus. (L–O) P13 mutant thymus. Stained with H&E for histology (A, E, H, L), BrdU (B, I, M), β-catenin (C, F, J, N), and K14 (D, G, K, O). (B) Actively dividing thymocytes are visible at the superficial edge of cortex of normal P3 thymus. Note the progression of histological abnormalities in the mutant thymus from mild P3, severe P3 to P13 (A, E, H, L). Scale bars, 20 μm. The histological abnormalities of thymus were evident as early as P3 in KA mutants (Figure 6E and 6H). The thymus was made of two lobules as in the normal mice but the mutant thymus was significantly smaller in size than that of the age-matched controls (Figure 2G). Interestingly, variations in the phenotypic severity of the mutant pups at P3 were prominently reflected in the extent of histological abnormalities of thymus. A P3 KA mutant pup that showed milder phenotype with a comparable body weight to its normal littermates (Figure 2A, M2) showed milder thymus abnormalities (Figure 6E) compared to its more severe mutant littermate (Figure 2A, M1; Figure 6H). The milder P3 mutant thymus was already much smaller in size compared to those of normal littermates (data not shown) but two epithelial compartments of thymus were histologically still distinguishable, with colonization of thymocytes evident in the cortex. However, there were small populations of lightly stained cells by H&E extending from the edge of the outer cortex towards inner medulla (Figure 6E), and these cells showed intense nuclear β-catenin staining whereas the rest of the medullary cells showed diffuse β-catenin staining pattern similar to that of the control (Figure 6F). Localization of K14 was limited to a few cells in the medulla and some overlapped with K8 localization (Figure 6G). In the other P3 mutant thymus the distinct thymic epithelial compartments have been lost completely, and only a few lymphocytes were remaining at the edges and some in the middle (Figure 6H). Proliferative activities were no longer observed in thymocytes as prominently as in the normal thymus, but the epithelial cells seemed to be forming concentric structures (Figure 6I). Unlike in the normal or mild mutant thymi, the severe P3 mutant thymus showed extensive K14 expression that overlapped with K8 expression (Figure 6K). These cells were more like basal cells of the skin than TECs and were adjacent to the most immature looking cells that were showing strong nuclear and cytoplasmic β-catenin staining (Figure 6J). The nuclear staining of β-catenin was not observed in the normal age-matched thymus (Figure 6C). Most notably, the K14 and β-catenin staining patterns were mutually exclusive (Figure 6J and 6K). At P10–P13, the mutant thymus consisted of numerous enlarged Hassall's corpuscle–like structures, made of arrays of K14- and K8-expressing keratinizing epithelial cells surrounding large keratin deposits (Figure 6L and 6O). There were numerous neutrophils and macrophages infiltrating the thymus in response to these keratins; hence, these structures could be called pyogranuloma. Varying degrees of differentiation-specific markers depending on the age of mice, in this case K1 and involucrin that are normally present only in Hassall's corpuscles, were also detected in mutant thymi (Figure S3). In these mice no thymocytes were detectable. BrdU incorporation was only observed in very few keratinizing epithelial cells, looking somewhat similar to the pattern of mature skin (Figure 6M). The diffuse expression of β-catenin was also present in these epithelial cells, and at this age fewer cells were positive for nuclear β-catenin staining (Figure 6N). As in the younger mutant mice, however, nuclear localization of β-catenin was only observed in K14-negative cells that looked like undifferentiated basal cells. In older P17 mice, the histopathology and keratin expression pattern of the mutant thymus was similar to that of P13 except for the fact that β-catenin expression became increasingly diffuse and appeared to colocalize with K8/K14 expression (data not shown). This coincided with fewer immature cells in the older mutant thymus. Collectively, these results suggest that loss of Apc and consequent stabilization of β-catenin in K14-expressing TECs lead to their aberrant proliferation and differentiation to keratinocytes, causing massive squamous metaplasia, rather than to form either medullary or cortical TECs. Loss of proper TEC compartments consequently resulted in loss of thymocytes for maturation and the mice to be “athymic.” Discussion Apc
T18948 37388-37409 GO:0016055 denotes Wnt signaling pathway
T18949 37466-37471 NCBITaxon:9606 denotes Human
T18950 37494-37497 PR:000004122 denotes APC
T18951 37565-37575 UBERON:0012652 denotes colorectal
T18952 37625-37635 UBERON:0012652 denotes colorectal
T18953 37678-37682 UBERON:0000104 denotes life
T18954 37787-37797 UBERON:0012652 denotes colorectal
T18955 37812-37823 NCBITaxon:1 denotes individuals
T18956 37841-37848 UBERON:0001155 denotes colonic
T18957 37875-37903 UBERON:0004908 denotes upper gastrointestinal tract
T18958 37942-37968 UBERON:0001782 denotes retinal pigment epithelium
T18959 37950-37957 CHEBI:26130 denotes pigment
T18960 38003-38012 UBERON:0002397 denotes maxillary
T18961 38017-38025 UBERON:0004288 denotes skeletal
T18962 38026-38031 UBERON:0001474 denotes bones
T18963 38037-38043 UBERON:0001091 denotes dental
T18964 38095-38099 NCBITaxon:10088 denotes mice
T18965 38104-38107 PR:000004122 denotes Apc
T18966 38152-38167 UBERON:0002108 denotes small intestine
T18967 38184-38191 UBERON:0000922 denotes embryos
T18968 38192-38195 GO:0016265 denotes die
T18969 38203-38215 GO:0007369 denotes gastrulation
T18970 38259-38262 PR:000004122 denotes Apc
T18971 38271-38278 UBERON:0000479 denotes tissues
T18972 38290-38312 UBERON:0001555 denotes gastrointestinal tract
T18973 38320-38324 UBERON:0000104 denotes life
T18974 38328-38335 NCBITaxon:33208 denotes animals
T18975 38358-38367 UBERON:0000922 denotes embryonic
T18976 38394-38397 PR:000004122 denotes Apc
T18977 38426-38431 NCBITaxon:10088 denotes mouse
T18978 38462-38468 SO:0001023 denotes allele
T18979 38472-38475 PR:000004122 denotes Apc
T18980 38477-38480 PR:000004122 denotes Apc
T18981 38494-38498 SO:0000147 denotes exon
T18982 38509-38512 PR:000004122 denotes Apc
T18983 38516-38523 SO:0000357 denotes flanked
T18984 38527-38541 SO:0000346 denotes loxP sequences
T18985 38558-38562 NCBITaxon:10088 denotes mice
T18986 38583-38589 SO:0001023 denotes allele
T18987 38637-38641 NCBITaxon:10088 denotes mice
T18988 38677-38680 PR:000004122 denotes Apc
T18989 38686-38692 UBERON:0000479 denotes tissue
T18990 38785-38788 PR:000004122 denotes Apc
T18991 38789-38793 SO:0000704 denotes gene
T18992 38808-38815 GO:0010467 denotes express
T18993 38816-38819 PR:000009454 denotes K14
T18994 38832-38836 NCBITaxon:10088 denotes mice
T18995 38865-38868 PR:000004122 denotes Apc
T18996 38872-38878 SO:0001023 denotes allele
T18997 38893-38896 PR:000009454 denotes K14
T18998 38901-38910 SO:0000902 denotes transgene
T18999 38918-38922 NCBITaxon:10088 denotes mice
T19000 38944-38948 GO:0016265 denotes died
T19001 38985-38989 UBERON:0001037 denotes hair
T19002 38991-38996 UBERON:0001091 denotes tooth
T19003 39002-39008 UBERON:0002370 denotes thymus
T21686 39022-39025 PR:000004122 denotes Apc
T21687 39030-39043 UBERON:0002073 denotes Hair Follicle
T21688 39030-39057 GO:0031069 denotes Hair Follicle Morphogenesis
T21689 39076-39089 UBERON:0002073 denotes hair follicle
T21690 39076-39101 GO:0001942 denotes hair follicle development
T21691 39179-39189 UBERON:0000483 denotes epithelium
T21692 39278-39287 CHEBI:36357 denotes molecules
T21693 39385-39406 GO:0016055 denotes Wnt signaling pathway
T21694 39414-39420 UBERON:0002067 denotes dermis
T21695 39505-39515 UBERON:0000483 denotes epithelial
T21696 39516-39525 PR:000002198 denotes β-catenin
T21697 39540-39550 GO:0010467 denotes expression
T21698 39611-39620 PR:000002198 denotes β-catenin
T21699 39632-39642 GO:0010467 denotes expression
T21700 39646-39650 PR:000009751 denotes Lef1
T21701 39686-39691 NCBITaxon:10088 denotes mouse
T21702 39747-39756 PR:000002198 denotes β-catenin
T21703 39776-39780 PR:000009751 denotes Lef1
T21704 39800-39810 GO:0010467 denotes expression
T21705 39818-39827 CHEBI:35222 denotes inhibitor
T21706 39828-39832 PR:000006499 denotes Dkk1
T21707 39860-39869 PR:000002198 denotes β-catenin
T21708 39873-39882 UBERON:0007376 denotes epidermis
T21709 39903-39912 UBERON:0010419 denotes vibrissae
T21710 39922-39928 UBERON:0010509 denotes pelage
T21711 39942-39946 NCBITaxon:10088 denotes mice
T21712 39973-39976 PR:000009454 denotes K14
T21713 39984-39987 PR:000004122 denotes Apc
T21714 39996-40014 UBERON:0000924 denotes embryonic ectoderm
T21715 40083-40095 UBERON:0005086 denotes hair placode
T21716 40120-40133 GO:0009653 denotes morphogenesis
T21717 40205-40215 UBERON:0008281 denotes tooth buds
T21718 40286-40296 UBERON:0000483 denotes epithelial
T21719 40297-40306 PR:000002198 denotes β-catenin
T21720 40366-40369 PR:000004122 denotes Apc
T21721 40373-40389 _FRAGMENT denotes specification of
T21722 40411-40421 GO:0048866 denotes stem cells
T21723 40400-40410 _FRAGMENT denotes ectodermal
T21724 40416-40421 GO:0001715 denotes cells
T21725 40390-40410 UBERON:0000924 denotes embryonic ectodermal
T21726 40390-40399 _FRAGMENT denotes embryonic
T21727 40411-40421 CL:0002322 denotes stem cells
T21728 40416-40421 CL:0000221 denotes cells
T21729 40435-40448 UBERON:0002073 denotes hair follicle
T21730 40468-40471 PR:000004122 denotes Apc
T21731 40494-40503 PR:000002198 denotes β-catenin
T21732 40513-40516 PR:000004122 denotes Apc
T21733 40550-40560 GO:0010467 denotes expression
T21734 40564-40573 PR:000002198 denotes β-catenin
T21735 40577-40587 UBERON:0000924 denotes ectodermal
T21736 40577-40593 CL:0000221 denotes ectodermal cells
T21737 40605-40617 UBERON:0005086 denotes hair placode
T21738 40605-40627 GO:0060789 denotes hair placode formation
T21739 40686-40695 UBERON:0000922 denotes embryonic
T21740 40696-40705 UBERON:0007376 denotes epidermis
T21741 40721-40729 UBERON:0013623 denotes footpads
T21742 40746-40750 UBERON:0001037 denotes hair
T21743 40866-40870 NCBITaxon:10088 denotes mice
T21744 40900-40903 PR:000009454 denotes K14
T21745 40924-40928 NCBITaxon:10088 denotes mice
T21746 40929-40939 GO:0010467 denotes expressing
T21747 40947-40956 PR:000002198 denotes β-catenin
T21748 40967-40974 GO:0065007 denotes control
T21749 40978-40981 PR:000009454 denotes K14
T21750 40982-40990 SO:0000167 denotes promoter
T21751 41000-41003 PR:000009454 denotes K14
T21752 41004-41008 PR:000009751 denotes Lef1
T21753 41020-41024 NCBITaxon:10088 denotes mice
T21754 41056-41060 NCBITaxon:10088 denotes mice
T21755 41095-41098 PR:000009454 denotes K14
T21756 41099-41103 PR:000009751 denotes Lef1
T21757 41104-41108 NCBITaxon:10088 denotes mice
T21758 41118-41121 PR:000009454 denotes K14
T21759 41142-41146 NCBITaxon:10088 denotes mice
T21760 41175-41179 NCBITaxon:10088 denotes mice
T21761 41240-41243 PR:000009454 denotes K14
T21762 41259-41262 PR:000009454 denotes K14
T21763 41283-41287 NCBITaxon:10088 denotes mice
T21764 41312-41316 NCBITaxon:10088 denotes mice
T21765 41342-41351 UBERON:0010166 denotes hair coat
T21766 41393-41398 UBERON:0001037 denotes hairs
T21767 41428-41431 PR:000009454 denotes K14
T21768 41432-41436 PR:000009751 denotes Lef1
T21769 41437-41441 NCBITaxon:10088 denotes mice
T21770 41454-41457 PR:000009454 denotes K14
T21771 41467-41471 NCBITaxon:10088 denotes mice
T21772 41473-41482 UBERON:0000922 denotes embryonic
T21773 41473-41482 _FRAGMENT denotes embryonic
T21774 41497-41510 GO:0048598 denotes morphogenesis
T21775 41483-41496 UBERON:0002073 denotes hair follicle
T21776 41483-41510 GO:0031069 denotes hair follicle morphogenesis
T21777 41566-41573 GO:0007567 denotes natally
T21778 41697-41700 PR:000009454 denotes K14
T21779 41701-41709 SO:0000167 denotes promoter
T21780 41742-41752 GO:0010467 denotes expression
T21781 41844-41854 GO:0010467 denotes expression
T21782 41858-41866 SO:0000167 denotes promoter
T21783 41867-41876 SO:0000902 denotes transgene
T21784 41901-41905 NCBITaxon:10088 denotes mice
T21785 41967-41983 SO:0000366 denotes integration site
T21786 41991-42000 SO:0000902 denotes transgene
T21787 42008-42013 NCBITaxon:10088 denotes mouse
T21788 42014-42020 SO:0001026 denotes genome
T21789 42039-42062 SO:0000366 denotes location of integration
T21790 42110-42119 SO:0000902 denotes transgene
T21791 42207-42220 GO:0009790 denotes embryogenesis
T21792 42257-42267 GO:0010467 denotes expression
T21793 42275-42278 PR:000009454 denotes K14
T21794 42288-42297 SO:0000902 denotes transgene
T21795 42324-42332 SO:0000167 denotes promoter
T21796 42399-42402 PR:000009454 denotes K14
T21797 42418-42422 NCBITaxon:10088 denotes mice
T21798 42451-42454 PR:000009454 denotes K14
T21799 42486-42489 PR:000004122 denotes Apc
T21800 42490-42494 SO:0000704 denotes gene
T21801 42562-42575 UBERON:0002073 denotes hair follicle
T21802 42562-42588 GO:0031069 denotes hair follicle morphgenesis
T21803 42672-42682 GO:0010467 denotes expression
T21804 42686-42695 SO:0000902 denotes transgene
T21805 42715-42729 _FRAGMENT denotes basal cells of
T21806 42734-42743 CL:0002187 denotes epidermis
T21807 42721-42729 _FRAGMENT denotes cells of
T21808 42752-42773 CL:0002561 denotes ORS of hair follicles
T21809 42734-42743 UBERON:0007376 denotes epidermis
T21810 42752-42773 UBERON:0005942 denotes ORS of hair follicles
T21811 42785-42788 PR:000009454 denotes K14
T21812 42789-42797 SO:0000167 denotes promoter
T21813 42813-42823 GO:0010467 denotes expression
T21814 42827-42836 SO:0000902 denotes transgene
T21815 42871-42874 PR:000009454 denotes K14
T21816 42875-42885 GO:0010467 denotes expressing
T21817 42945-42948 PR:000009454 denotes K14
T21818 42974-42977 PR:000004122 denotes Apc
T21819 42994-42997 PR:000004122 denotes Apc
T21820 43019-43022 PR:000009454 denotes K14
T21821 43023-43031 SO:0000167 denotes promoter
T21822 43067-43078 UBERON:0000119 denotes cell layers
T21823 43101-43104 PR:000009454 denotes K14
T21824 43105-43113 SO:0000167 denotes promoter
T21825 43164-43184 UBERON:0010402 denotes suprabasal epidermis
T21826 43200-43210 UBERON:0000483 denotes epithelium
T21827 43218-43231 UBERON:0002073 denotes hair follicle
T21828 43250-43259 PR:000002198 denotes β-catenin
T21829 43387-43396 PR:000002198 denotes β-catenin
T21830 43397-43407 GO:0010467 denotes expression
T21831 43418-43420 PR:000009450 denotes K1
T21832 43465-43470 GO:0007567 denotes natal
T21833 43527-43530 PR:000004122 denotes Apc
T21834 43562-43571 PR:000002198 denotes β-catenin
T21835 43590-43593 PR:000009454 denotes K14
T21836 43594-43604 GO:0010467 denotes expressing
T21837 43627-43636 PR:000002198 denotes β-catenin
T21838 43637-43647 GO:0010467 denotes expression
T21839 43664-43687 GO:0001709 denotes cell fate determination
T21840 43711-43722 CL:0000646 denotes basal cells
T21841 43807-43810 PR:000004122 denotes Apc
T21842 43870-43879 PR:000002198 denotes β-catenin
T21843 43973-43977 NCBITaxon:10088 denotes mice
T21844 44011-44015 NCBITaxon:10088 denotes mice
T21845 44089-44102 UBERON:0002073 denotes hair follicle
T21846 44089-44116 GO:0031069 denotes hair follicle morphogenesis
T21847 44118-44121 PR:000009454 denotes K14
T21848 44137-44140 PR:000004122 denotes Apc
T21849 44170-44180 UBERON:0008281 denotes tooth buds
T21850 44192-44206 UBERON:0002073 denotes hair follicles
T21851 44273-44283 UBERON:0000483 denotes epithelium
T21852 44288-44298 UBERON:0003104 denotes mesenchyme
T21853 44344-44354 UBERON:0008281 denotes tooth buds
T21854 44364-44371 NCBITaxon:33208 denotes animals
T21855 44375-44385 GO:0010467 denotes expressing
T21856 44386-44390 PR:000009751 denotes Lef1
T21857 44437-44442 GO:0007567 denotes birth
T21858 44469-44472 PR:000004122 denotes Apc
T21859 44503-44512 UBERON:0000922 denotes embryonic
T21860 44503-44512 _FRAGMENT denotes embryonic
T21861 44519-44530 GO:0009790 denotes development
T21862 44513-44518 UBERON:0001091 denotes tooth
T21863 44562-44565 PR:000014841 denotes Shh
T21864 44566-44576 GO:0010467 denotes expression
T21865 44586-44595 UBERON:0000922 denotes embryonic
T21866 44596-44611 UBERON:0002424 denotes oral epithelium
T21867 44674-44684 UBERON:0008281 denotes tooth buds
T21868 44739-44744 UBERON:0001091 denotes teeth
T21869 44779-44783 NCBITaxon:10088 denotes mice
T21870 44793-44798 UBERON:0001091 denotes tooth
T21871 44824-44829 UBERON:0001091 denotes tooth
T21872 44863-44867 NCBITaxon:10088 denotes mice
T21873 44912-44916 NCBITaxon:10088 denotes mice
T21874 44925-44932 GO:0007567 denotes natally
T21875 44960-44964 NCBITaxon:10088 denotes mice
T21876 45042-45048 UBERON:0000062 denotes organs
T21877 45055-45059 NCBITaxon:10088 denotes mice
T21878 45202-45206 CHEBI:33290 denotes food
T21879 45216-45223 UBERON:0000945 denotes stomach
T21880 45262-45266 GO:0016265 denotes died
T21881 45394-45399 UBERON:0001091 denotes teeth
T21882 45479-45485 GO:0001967 denotes nursed
T21883 45530-45535 UBERON:0001091 denotes teeth
T21884 45564-45569 GO:0016265 denotes death
T21885 45625-45630 UBERON:0001091 denotes teeth
T21886 45635-45649 UBERON:0001911 denotes mammary glands
T21887 45672-45676 NCBITaxon:10088 denotes mice
T21888 45690-45694 PR:000009751 denotes Lef1
T21889 45711-45721 GO:0010467 denotes expressing
T21890 45722-45726 PR:000006499 denotes Dkk1
T21891 45845-45854 UBERON:0008281 denotes tooth bud
T21892 45894-45899 UBERON:0001091 denotes teeth
T21893 45904-45908 NCBITaxon:10088 denotes mice
T21894 45943-45947 UBERON:0000104 denotes life
T21895 46007-46016 PR:000002198 denotes β-catenin
T21896 46043-46048 UBERON:0001091 denotes tooth
T25062 46076-46079 PR:000004122 denotes Apc
T25063 46084-46090 UBERON:0002370 denotes Thymus
T25064 46084-46104 GO:0048538 denotes Thymus Organogenesis
T25065 46137-46140 PR:000009454 denotes K14
T25066 46156-46159 PR:000004122 denotes Apc
T25067 46180-46186 UBERON:0002370 denotes thymus
T25068 46311-46320 CL:0000893 denotes thymocyte
T25069 46347-46351 NCBITaxon:10088 denotes mice
T25070 46353-46359 UBERON:0002370 denotes thymic
T25071 46404-46409 UBERON:0007023 denotes adult
T25072 46410-46416 UBERON:0002370 denotes thymus
T25073 46417-46420 PR:000009454 denotes K14
T25074 46421-46431 GO:0010467 denotes expression
T25075 46455-46457 PR:000009481 denotes K5
T25076 46474-46483 UBERON:0000958 denotes medullary
T25077 46474-46488 CL:0002365 denotes medullary TECs
T25078 46518-46520 PR:000009481 denotes K5
T25079 46522-46526 CL:0002293 denotes TECs
T25080 46534-46540 UBERON:0001851 denotes cortex
T25081 46551-46558 UBERON:0001851 denotes cortico
T25082 46559-46568 UBERON:0000958 denotes medullary
T25083 46622-46625 PR:000009454 denotes K14
T25084 46627-46631 CL:0002293 denotes TECs
T25085 46641-46648 GO:0010467 denotes express
T25086 46649-46651 PR:000009495 denotes K8
T25087 46683-46692 UBERON:0000958 denotes medullary
T25088 46711-46713 PR:000009495 denotes K8
T25089 46714-46717 PR:000009454 denotes K14
T25090 46741-46743 PR:000009495 denotes K8
T25091 46744-46747 PR:000009454 denotes K14
T25092 46824-46830 UBERON:0002370 denotes thymus
T25093 46831-46834 PR:000009454 denotes K14
T25094 46835-46845 GO:0010467 denotes expression
T25095 46873-46882 UBERON:0000958 denotes medullary
T25096 46873-46887 CL:0002365 denotes medullary TECs
T25097 46909-46911 PR:000009495 denotes K8
T25098 46912-46922 GO:0010467 denotes expression
T25099 46948-46952 CL:0002293 denotes TECs
T25100 47028-47037 GO:0010467 denotes expressed
T25101 47050-47054 CL:0002293 denotes TECs
T25102 47206-47212 UBERON:0002370 denotes thymus
T25103 47299-47305 UBERON:0002370 denotes thymus
T25104 47318-47323 UBERON:0002370 denotes thymi
T25105 47387-47390 PR:000009454 denotes K14
T25106 47440-47446 UBERON:0002370 denotes thymus
T25107 47496-47503 GO:0005634 denotes nuclear
T25108 47504-47513 PR:000002198 denotes β-catenin
T25109 47544-47554 GO:0010467 denotes expressing
T25110 47555-47558 PR:000009454 denotes K14
T25111 47574-47591 UBERON:0003846 denotes thymic epithelial
T25112 47639-47645 UBERON:0002370 denotes thymus
T25113 47707-47716 UBERON:0000958 denotes medullary
T25114 47707-47716 _FRAGMENT denotes medullary
T25115 47730-47734 CL:0002365 denotes TECs
T25116 47721-47729 UBERON:0001851 denotes cortical
T25117 47721-47734 CL:0002364 denotes cortical TECs
T25118 47739-47748 CL:0000893 denotes thymocyte
T25119 47817-47820 PR:000009454 denotes K14
T25120 47828-47831 PR:000004122 denotes Apc
T25121 47858-47865 GO:0005634 denotes nuclear
T25122 47866-47875 PR:000002198 denotes β-catenin
T25123 47880-47882 PR:000009495 denotes K8
T25124 47883-47886 PR:000009454 denotes K14
T25125 47904-47914 UBERON:0000483 denotes epithelial
T25126 47904-47920 CL:0000066 denotes epithelial cells
T25127 47968-47981 GO:0008283 denotes proliferation
T25128 48023-48026 CL:0002293 denotes TEC
T25129 48051-48060 PR:000002198 denotes β-catenin
T25130 48061-48071 GO:0010467 denotes expression
T25131 48110-48120 UBERON:0000483 denotes epithelial
T25132 48110-48126 CL:0000066 denotes epithelial cells
T25133 48134-48141 GO:0005634 denotes nuclear
T25134 48159-48161 PR:000009495 denotes K8
T25135 48162-48165 PR:000009454 denotes K14
T25136 48216-48226 UBERON:0000483 denotes epithelial
T25137 48216-48232 CL:0000066 denotes epithelial cells
T25138 48303-48314 CL:0000775 denotes neutrophils
T25139 48319-48330 CL:0000235 denotes macrophages
T25140 48343-48353 UBERON:0000483 denotes epithelial
T25141 48343-48359 CL:0000066 denotes epithelial cells
T25142 48389-48399 CL:0000893 denotes thymocytes
T25143 48475-48478 PR:000004122 denotes Apc
T25144 48482-48486 CL:0002293 denotes TECs
T25145 48508-48515 GO:0005634 denotes nuclear
T25146 48532-48541 PR:000002198 denotes β-catenin
T25147 48602-48615 CL:0000312 denotes keratinocytes
T25148 48621-48630 GO:0010467 denotes expressed
T25149 48636-48639 PR:000009454 denotes K14
T25150 48644-48646 PR:000009495 denotes K8
T25151 48663-48674 CL:0000646 denotes basal cells
T25152 48699-48702 CL:0002293 denotes TEC
T25153 48755-48768 CL:0000312 denotes keratinocytes
T25154 48792-48809 UBERON:0003846 denotes thymic epithelial
T25155 48916-48927 CL:0000775 denotes neutrophils
T25156 48932-48943 CL:0000235 denotes macrophages
T25157 48962-48968 UBERON:0002370 denotes thymus
T25158 48985-48995 UBERON:0000483 denotes epithelial
T25159 49050-49056 UBERON:0002370 denotes thymus
T25160 49086-49096 CL:0000893 denotes thymocytes
T25161 49098-49101 PR:000009454 denotes K14
T25162 49117-49120 PR:000004122 denotes Apc
T25163 49149-49159 GO:0010467 denotes expression
T25164 49163-49172 PR:000002198 denotes β-catenin
T25165 49176-49180 CL:0002293 denotes TECs
T25166 49222-49232 UBERON:0000483 denotes epithelial
T25167 49222-49237 CL:0000066 denotes epithelial cell
T25168 49290-49298 UBERON:0001851 denotes cortical
T25169 49290-49298 _FRAGMENT denotes cortical
T25170 49312-49316 CL:0002364 denotes TECs
T25171 49302-49311 UBERON:0000958 denotes medullary
T25172 49302-49316 CL:0002365 denotes medullary TECs
T25173 49348-49357 CL:0000893 denotes thymocyte
T25174 49422-49432 CL:0000893 denotes thymocytes
T25175 49447-49453 UBERON:0002370 denotes thymus
T25176 49491-49501 GO:0010467 denotes expression
T25177 49554-49557 CL:0002293 denotes TEC
T25178 49582-49585 PR:000004122 denotes Apc
T25179 49598-49604 UBERON:0002370 denotes thymic
T25180 49598-49616 GO:0048538 denotes thymic development
T25181 49642-49651 CL:0000893 denotes thymocyte
T25182 49669-49672 PR:000004122 denotes Apc
T25183 49707-49710 PR:000004122 denotes Apc
T25184 49723-49727 NCBITaxon:10088 denotes mice
T25185 49750-49754 NCBITaxon:10088 denotes mice
T25186 49770-49773 PR:000009454 denotes K14
T25187 49781-49784 CL:0002293 denotes TEC
T25188 49802-49805 PR:000004122 denotes Apc
T25189 49846-49852 UBERON:0002370 denotes thymus
T25190 49846-49864 GO:0048538 denotes thymus development
T25191 49877-49887 CL:0000893 denotes thymocytes
T25192 49900-49904 CL:0002293 denotes TECs
T25193 49929-49935 UBERON:0001091 denotes dental
T25194 49986-49991 UBERON:0001091 denotes teeth
T25195 50032-50036 NCBITaxon:10088 denotes mice
T25196 50107-50110 PR:000004122 denotes APC
T25197 50152-50158 UBERON:0001091 denotes odonto
T25198 50159-50173 UBERON:0000165 denotes stomatological
T25199 50389-50394 NCBITaxon:10088 denotes mouse
T25200 50440-50443 PR:000004122 denotes Apc
T25201 50465-50478 UBERON:0000467 denotes organ systems
T25202 50540-50545 NCBITaxon:9606 denotes human
T25203 50598-50601 PR:000004122 denotes Apc
T25204 50605-50608 PR:000009454 denotes K14
T25205 50609-50619 GO:0010467 denotes expressing
T25206 50620-50629 UBERON:0000922 denotes embryonic
T25207 50620-50635 CL:0002321 denotes embryonic cells
T25208 50652-50665 GO:0009653 denotes morphogenesis
T25209 50682-50692 UBERON:0004529 denotes appendages
T25210 50704-50718 UBERON:0002073 denotes hair follicles
T25211 50723-50728 UBERON:0001091 denotes teeth
T25212 50743-50749 UBERON:0002370 denotes thymus
T25213 50743-50762 GO:0048538 denotes thymus organogensis
T25214 50784-50791 SO:0000704 denotes genetic
T25215 50806-50816 GO:0010467 denotes expression
T25216 50820-50823 PR:000004122 denotes Apc
T25217 50841-50851 GO:0065007 denotes regulation
T25218 50882-50888 UBERON:0000062 denotes organs
T25219 50902-50912 UBERON:0000483 denotes epithelial
T25220 50913-50924 UBERON:0003104 denotes mesenchymal
T26491 50979-50996 SO:0001644 denotes targeting vectors
T26492 51012-51015 PR:000004122 denotes Apc
T26493 51035-51038 SO:0000153 denotes BAC
T26494 51091-51094 PR:000004122 denotes Apc
T26495 51110-51116 SO:0000204 denotes 5′ UTR
T26496 51121-51125 SO:0000147 denotes exon
T26497 51225-51228 SO:0000153 denotes BAC
T26498 51275-51282 SO:0001026 denotes genomic
T26499 51305-51308 PR:000004122 denotes Apc
T26500 51309-51314 SO:0000147 denotes exons
T26501 51356-51362 SO:0000440 denotes vector
T26502 51375-51384 SO:0000346 denotes loxP site
T26503 51405-51411 SO:0000188 denotes intron
T26504 51427-51431 SO:0000346 denotes loxP
T26505 51432-51435 SO:0000350 denotes FRT
T26506 51444-51447 SO:0000350 denotes FRT
T26507 51458-51466 SO:0005853 denotes cassette
T26508 51488-51491 PR:000004122 denotes Apc
T26509 51492-51496 SO:0000704 denotes gene
T27003 51511-51524 _FRAGMENT denotes Generation of
T27004 51535-51540 GO:0048468 denotes cells
T27005 51525-51528 PR:000004122 denotes Apc
T27006 51532-51540 CL:0002322 denotes ES cells
T27007 51545-51549 NCBITaxon:10088 denotes mice
T27008 51566-51583 SO:0001644 denotes targeting vectors
T27009 51623-51631 CL:0002322 denotes ES cells
T27010 51663-51667 CHEBI:42768 denotes G418
T27011 51678-51680 CL:0002322 denotes ES
T27012 51716-51720 SO:0000704 denotes gene
T27013 51890-51899 SO:0000346 denotes loxP site
T27014 51918-51926 SO:0005853 denotes cassette
T27015 51932-51934 CL:0002322 denotes ES
T27016 51955-51958 PR:000004122 denotes Apc
T27017 52006-52017 UBERON:0000358 denotes blastocysts
T27018 52040-52044 NCBITaxon:10088 denotes mice
T27019 52065-52072 CL:0002322 denotes ES cell
T27020 52165-52172 SO:0001026 denotes genomic
T27021 52203-52207 UBERON:0002415 denotes tail
T27022 52363-52367 NCBITaxon:10088 denotes mice
T27023 52384-52388 NCBITaxon:10088 denotes mice
T27024 52403-52411 SO:0005853 denotes cassette
T27025 52443-52446 SO:0000350 denotes FRT
T27026 52482-52486 NCBITaxon:10088 denotes mice
T27027 52502-52505 PR:000004122 denotes Apc
T27028 52509-52515 SO:0001023 denotes allele
T27029 52517-52520 PR:000004122 denotes Apc
T27030 52537-52541 NCBITaxon:10088 denotes mice
T27031 52587-52591 NCBITaxon:10088 denotes mice
T27404 52669-52672 PR:000004122 denotes Apc
T27405 52677-52681 NCBITaxon:10088 denotes mice
T27406 52683-52686 PR:000004122 denotes Apc
T27407 52703-52707 NCBITaxon:10088 denotes mice
T27408 52738-52742 NCBITaxon:10088 denotes mice
T27409 52764-52768 NCBITaxon:10088 denotes mice
T27410 52774-52781 GO:0010467 denotes express
T27411 52789-52801 UBERON:0019248 denotes early embryo
T27412 52824-52827 PR:000004122 denotes Apc
T27413 52828-52834 SO:0001023 denotes allele
T27414 52919-52922 PR:000004122 denotes Apc
T27415 52929-52933 NCBITaxon:10088 denotes mice
T27656 53002-53005 PR:000009454 denotes K14
T27657 53011-53014 PR:000004122 denotes Apc
T27658 53022-53026 NCBITaxon:10088 denotes mice
T27659 53032-53036 NCBITaxon:10088 denotes mice
T27660 53087-53090 PR:000004122 denotes Apc
T27661 53107-53111 NCBITaxon:10088 denotes mice
T27662 53168-53171 PR:000009454 denotes K14
T27663 53187-53191 NCBITaxon:10088 denotes mice
T27664 53210-53213 PR:000009454 denotes K14
T27665 53219-53222 PR:000004122 denotes Apc
T27666 53233-53237 NCBITaxon:10088 denotes mice
T27667 53276-53279 PR:000004122 denotes Apc
T27668 53335-53338 PR:000004122 denotes Apc
T27669 53375-53378 PR:000009454 denotes K14
T27670 53388-53392 NCBITaxon:10088 denotes mice
T28202 53454-53458 NCBITaxon:10088 denotes mice
T28203 53460-53467 SO:0001026 denotes Genomic
T28204 53477-53484 _FRAGMENT denotes tips of
T28205 53491-53496 UBERON:0010162 denotes tails
T28206 53485-53490 NCBITaxon:10088 denotes mouse
T28207 53580-53587 SO:0000112 denotes primers
T28208 53589-53592 PR:000004122 denotes Apc
T28209 53630-53633 PR:000004122 denotes Apc
T28210 53685-53687 SO:0000028 denotes bp
T28211 53696-53698 SO:0000028 denotes bp
T28212 53743-53746 PR:000004122 denotes Apc
T28213 53750-53756 SO:0001023 denotes allele
T28214 53814-53817 PR:000004122 denotes Apc
T28215 53818-53824 SO:0001023 denotes allele
T28216 53826-53829 PR:000004122 denotes Apc
T28217 53839-53845 SO:0000112 denotes primer
T28218 53846-53849 PR:000004122 denotes Apc
T28219 53903-53906 PR:000004122 denotes Apc
T28220 53931-53933 SO:0000028 denotes bp
T28221 53943-53950 SO:0000112 denotes Primers
T28222 54049-54058 SO:0000902 denotes transgene
T28223 54093-54095 SO:0000028 denotes bp
T28224 54169-54173 CHEBI:9754 denotes Tris
T28225 54174-54177 CHEBI:17883 denotes HCl
T28226 54194-54197 CHEBI:32588 denotes KCl
T28227 54206-54211 CHEBI:6636 denotes MgCl2
T28228 54240-54246 SO:0000112 denotes primer
T28732 54606-54613 UBERON:0000922 denotes embryos
T28733 54655-54660 CHEBI:75055 denotes X-gal
T28734 54670-54673 CHEBI:60004 denotes mix
T28735 54692-54697 CHEBI:37586 denotes NaPO4
T28736 54706-54711 CHEBI:6636 denotes MgCl2
T28737 54718-54727 CHEBI:30060 denotes K3Fe(CN)6
T28738 54734-54743 CHEBI:30059 denotes K4Fe(CN)6
T28739 54757-54762 CHEBI:75055 denotes X-gal
T28740 54829-54838 UBERON:0007376 denotes epidermal
T28741 54852-54860 CHEBI:75958 denotes solution
T28742 54872-54881 UBERON:0007376 denotes epidermis
T28743 54990-54997 UBERON:0000922 denotes embryos
T29051 55131-55139 UBERON:0004288 denotes Skeletal
T29052 55288-55307 CHEBI:32035 denotes potassium hydroxide
T29053 55309-55312 CHEBI:32035 denotes KOH
T29054 55364-55372 CHEBI:75958 denotes solution
T29055 55379-55382 CHEBI:32035 denotes KOH
T29056 55414-55426 CHEBI:16866 denotes alizarin red
T29057 55533-55541 CHEBI:17754 denotes glycerin
T29444 55598-55604 UBERON:0000479 denotes tissue
T29445 55638-55644 UBERON:0000479 denotes tissue
T29446 55687-55693 SO:0001023 denotes allele
T29447 55766-55773 UBERON:0000479 denotes tissues
T29448 55880-55886 UBERON:0000479 denotes tissue
T29449 55909-55916 CHEBI:33893 denotes reagent
T29450 55935-55945 GO:0010467 denotes expression
T29451 55973-55976 PR:000004122 denotes Apc
T29452 55977-55984 SO:0001023 denotes alleles
T29453 56172-56177 UBERON:0002107 denotes liver
T29454 56182-56188 UBERON:0002370 denotes thymus
T29455 56212-56231 GO:0001171 denotes reverse-transcribed
T29456 56238-56245 SO:0000112 denotes primers
T29457 56246-56249 PR:000004122 denotes Apc
T29458 56283-56286 PR:000004122 denotes Apc
T29459 56334-56336 SO:0000028 denotes bp
T29460 56345-56347 SO:0000028 denotes bp
T29461 56376-56379 PR:000004122 denotes Apc
T29462 56383-56390 SO:0001023 denotes alleles
T29463 56395-56398 PR:000004122 denotes Apc
T29464 56403-56409 SO:0001023 denotes allele
T29744 56426-56430 CHEBI:472552 denotes BrdU
T29745 56441-56445 NCBITaxon:10088 denotes Mice
T29746 56465-56477 UBERON:0001179 denotes peritoneally
T29747 56520-56524 CHEBI:472552 denotes BrdU
T29748 56567-56572 GO:0016265 denotes death
T29749 56574-56580 UBERON:0000479 denotes Tissue
T30363 56695-56699 NCBITaxon:10088 denotes mice
T30364 56769-56772 CHEBI:16526 denotes CO2
T30365 56785-56789 NCBITaxon:10088 denotes Mice
T30366 56902-56909 CHEBI:33893 denotes reagent
T30367 57008-57016 CHEBI:75958 denotes solution
T30368 57076-57080 NCBITaxon:10088 denotes mice
T30369 57132-57139 UBERON:0000479 denotes tissues
T30370 57209-57219 UBERON:0000468 denotes whole body
T30371 57241-57249 CHEBI:75958 denotes solution
T30372 57286-57292 NCBITaxon:9989 denotes Rodent
T30373 57416-57422 UBERON:0000479 denotes tissue
T30374 57454-57460 CHEBI:27338 denotes xylene
T30375 57474-57481 CHEBI:30879 denotes alcohol
T30376 57540-57544 CHEBI:16240 denotes H2O2
T30377 57548-57556 CHEBI:17790 denotes methanol
T30378 57594-57599 CHEBI:15377 denotes water
T30379 57608-57615 CHEBI:59132 denotes antigen
T30380 57771-57781 GO:0042571 denotes antibodies
T30381 57813-57823 GO:0042571 denotes Antibodies
T30382 57834-57843 PR:000002198 denotes β-catenin
T30383 57848-57860 GO:0009293 denotes Transduction
T30384 57905-57915 PR:000009450 denotes keratins 1
T30385 57905-57913 _FRAGMENT denotes keratins
T30386 57917-57918 PR:000009481 denotes 5
T30387 57923-57925 PR:000009454 denotes 14
T30388 57927-57937 PR:000009167 denotes involucrin
T30389 57939-57947 PR:000009882 denotes loricrin
T30390 57996-58005 PR:000009495 denotes keratin 8
T30391 58042-58046 PR:000010425 denotes Ki67
T30392 58112-58116 CHEBI:472552 denotes BrdU
T30393 58126-58138 MOP:0000093 denotes Biotinylated
T30394 58149-58159 GO:0042571 denotes antibodies
T30395 58161-58167 NCBITaxon:9793 denotes donkey
T30396 58173-58179 NCBITaxon:9986 denotes rabbit
T30397 58184-58188 NCBITaxon:9925 denotes goat
T30398 58194-58199 NCBITaxon:10088 denotes mouse
T30399 58200-58203 GO:0071735 denotes IgG
T30400 58431-58442 CHEBI:51686 denotes hematoxylin
T30883 58453-58466 GO:0097617 denotes hybridization
T30884 58486-58489 NCBITaxon:10114 denotes rat
T30885 58490-58493 PR:000014841 denotes Shh
T30886 58531-58540 PR:000002198 denotes β-catenin
T30887 58624-58627 CHEBI:42098 denotes DIG
T30888 58684-58692 CHEBI:75958 denotes solution
R235 T2075 T2074 _lexicallyChainedTo nucleus,migration to
R236 T2100 T2099 _lexicallyChainedTo cell cycle,regulation of
R237 T2101 T2099 _lexicallyChainedTo apoptosis,regulation of
R238 T2136 T2135 _lexicallyChainedTo organs,morphogenesis of
R239 T2177 T2176 _lexicallyChainedTo stratified epithelia,cells of
R240 T2184 T2183 _lexicallyChainedTo organs,development of
R907 T4315 T4314 _lexicallyChainedTo cells,embryonic stem
R908 T4315 T4316 _lexicallyChainedTo cells,ES
R909 T4326 T4325 _lexicallyChainedTo sites,FLP recognition target
R910 T4326 T4327 _lexicallyChainedTo sites,FRT
R911 T4341 T4340 _lexicallyChainedTo sites,loxP
R1589 T7404 T7403 _lexicallyChainedTo epidermis,cells of
R1590 T7416 T7415 _lexicallyChainedTo thymus,medulla of
R1591 T7491 T7490 _lexicallyChainedTo molars,maxillary
R3033 T12205 T12204 _lexicallyChainedTo epidermis,basal layer of
R3034 T12215 T12214 _lexicallyChainedTo hair cycle,anagen phase of
R3035 T12244 T12243 _lexicallyChainedTo layers of epidermis,spinous
R3036 T12256 T12255 _lexicallyChainedTo hair follicle,ORS of
R3037 T12270 T12269 _lexicallyChainedTo hair follicles,ORS of
R3038 T12288 T12287 _lexicallyChainedTo cells,basal
R3039 T12338 T12337 _lexicallyChainedTo morphogenesis,embryonic
R4265 T14429 T14428 _lexicallyChainedTo salivary,epithelia of
R4266 T14430 T14429 _lexicallyChainedTo glands,salivary
R4267 T14431 T14428 _lexicallyChainedTo Hardarian glands,epithelia of
R4268 T14433 T14432 _lexicallyChainedTo glands,oral
R4553 T16831 T16830 _lexicallyChainedTo medulla,TECs of
R4554 T16836 T16835 _lexicallyChainedTo TEC,Cortical
R4555 T16947 T16946 _lexicallyChainedTo cells,keratinizing
R4556 T16963 T16962 _lexicallyChainedTo cells,keratinizing
R4557 T16996 T16995 _lexicallyChainedTo TECs,medullary
R5936 T21722 T21721 _lexicallyChainedTo stem cells,specification of
R5937 T21723 T21721 _lexicallyChainedTo ectodermal,specification of
R5938 T21724 T21723 _lexicallyChainedTo cells,ectodermal
R5939 T21727 T21726 _lexicallyChainedTo stem cells,embryonic
R5940 T21728 T21723 _lexicallyChainedTo cells,ectodermal
R5941 T21774 T21773 _lexicallyChainedTo morphogenesis,embryonic
R5942 T21806 T21805 _lexicallyChainedTo epidermis,basal cells of
R5943 T21808 T21807 _lexicallyChainedTo ORS of hair follicles,cells of
R5944 T21861 T21860 _lexicallyChainedTo development,embryonic
R7217 T25115 T25114 _lexicallyChainedTo TECs,medullary
R7218 T25170 T25169 _lexicallyChainedTo TECs,cortical
R8154 T27004 T27003 _lexicallyChainedTo cells,Generation of
R8500 T28205 T28204 _lexicallyChainedTo tails,tips of
R9142 T30386 T30385 _lexicallyChainedTo 5,keratins
R9143 T30387 T30385 _lexicallyChainedTo 14,keratins
R1 T439 T438 _lexicallyChainedTo Thymus,Development of
R2 T460 T459 _lexicallyChainedTo stratified epithelia,cells of
R3 T476 T475 _lexicallyChainedTo epithelia,oral

craft-sa-dev

Id Subject Object Predicate Lexical cue
T566 0-11 JJ denotes Adenomatous
T567 22-26 NN denotes Coli
T568 0-86 sentence denotes Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus
T569 12-21 NN denotes Polyposis
T570 36-44 VBN denotes Required
T571 27-28 -LRB- denotes (
T572 28-31 NN denotes APC
T573 31-32 -RRB- denotes )
T574 33-35 VBZ denotes Is
T575 45-48 IN denotes for
T576 49-55 JJ denotes Normal
T577 56-67 NN denotes Development
T578 68-70 IN denotes of
T579 71-75 NN denotes Skin
T580 76-79 CC denotes and
T581 80-86 NN denotes Thymus
T584 86-286 sentence denotes Role of APC in Skin and Its Appendages Abstract The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis.
T585 136-139 DT denotes The
T586 157-161 NN denotes gene
T587 140-145 NN denotes tumor
T588 146-156 NN denotes suppressor
T589 195-197 VBZ denotes is
T590 162-165 NN denotes Apc
T591 166-167 -LRB- denotes (
T592 167-178 FW denotes adenomatous
T593 189-193 FW denotes coli
T594 179-188 FW denotes polyposis
T595 193-194 -RRB- denotes )
T596 198-199 DT denotes a
T597 200-206 NN denotes member
T598 207-209 IN denotes of
T599 210-213 DT denotes the
T600 228-235 NN denotes pathway
T601 214-217 NN denotes Wnt
T602 218-227 NN denotes signaling
T603 236-240 WDT denotes that
T604 244-252 VBN denotes involved
T605 241-243 VBZ denotes is
T606 253-255 IN denotes in
T607 256-267 NN denotes development
T608 268-271 CC denotes and
T609 272-285 NN denotes tumorigenesis
T610 285-286 . denotes .
T611 286-406 sentence denotes Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality.
T612 287-299 JJ denotes Heterozygous
T613 300-308 NN denotes knockout
T614 309-313 NNS denotes mice
T615 322-326 VBP denotes have
T616 314-317 IN denotes for
T617 318-321 NN denotes Apc
T618 327-328 DT denotes a
T619 350-359 NN denotes phenotype
T620 329-334 NN denotes tumor
T621 335-349 NN denotes predisposition
T622 360-363 CC denotes and
T623 364-376 NN denotes homozygosity
T624 377-382 VBZ denotes leads
T625 383-385 IN denotes to
T626 386-395 JJ denotes embryonic
T627 396-405 NN denotes lethality
T628 405-406 . denotes .
T629 406-481 sentence denotes To understand the role of Apc in development we generated a floxed allele.
T630 407-409 TO denotes To
T631 410-420 VB denotes understand
T632 455-464 VBD denotes generated
T633 421-424 DT denotes the
T634 425-429 NN denotes role
T635 430-432 IN denotes of
T636 433-436 NN denotes Apc
T637 437-439 IN denotes in
T638 440-451 NN denotes development
T639 452-454 PRP denotes we
T640 465-466 DT denotes a
T641 474-480 NN denotes allele
T642 467-473 VBN denotes floxed
T643 480-481 . denotes .
T644 481-676 sentence denotes These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia.
T645 482-487 DT denotes These
T646 488-492 NNS denotes mice
T647 498-503 VBN denotes mated
T648 493-497 VBD denotes were
T649 504-508 IN denotes with
T650 509-510 DT denotes a
T651 511-517 NN denotes strain
T652 518-526 VBG denotes carrying
T653 527-530 NN denotes Cre
T654 531-542 NN denotes recombinase
T655 543-548 IN denotes under
T656 549-552 DT denotes the
T657 553-560 NN denotes control
T658 561-563 IN denotes of
T659 564-567 DT denotes the
T660 591-599 NN denotes promoter
T661 568-573 JJ denotes human
T662 574-581 NN denotes Keratin
T663 582-584 CD denotes 14
T664 585-586 -LRB- denotes (
T665 586-589 NN denotes K14
T666 589-590 -RRB- denotes )
T667 599-601 , denotes ,
T668 601-606 WDT denotes which
T669 607-609 VBZ denotes is
T670 610-616 JJ denotes active
T671 617-619 IN denotes in
T672 620-625 JJ denotes basal
T673 626-631 NNS denotes cells
T674 632-634 IN denotes of
T675 635-644 NN denotes epidermis
T676 645-648 CC denotes and
T677 649-654 JJ denotes other
T678 666-675 NNS denotes epithelia
T679 655-665 JJ denotes stratified
T680 675-676 . denotes .
T681 676-812 sentence denotes Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning.
T682 677-681 NNS denotes Mice
T683 753-757 VBD denotes were
T684 682-692 JJ denotes homozygous
T685 693-696 IN denotes for
T686 697-700 DT denotes the
T687 708-714 NN denotes allele
T688 701-707 VBN denotes floxed
T689 715-719 WDT denotes that
T690 725-730 VBP denotes carry
T691 720-724 RB denotes also
T692 731-734 DT denotes the
T693 743-752 NN denotes transgene
T694 735-738 NN denotes K14
T695 739-742 NN denotes cre
T696 738-739 HYPH denotes -
T697 758-764 JJ denotes viable
T698 765-768 CC denotes but
T699 769-772 VBD denotes had
T700 773-780 VBN denotes stunted
T701 781-787 NN denotes growth
T702 788-791 CC denotes and
T703 792-796 VBD denotes died
T704 797-803 IN denotes before
T705 804-811 NN denotes weaning
T706 811-812 . denotes .
T707 812-1039 sentence denotes Histological and immunochemical examinations revealed that K14-cre–mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia.
T708 813-825 JJ denotes Histological
T709 845-857 NNS denotes examinations
T710 826-829 CC denotes and
T711 830-844 JJ denotes immunochemical
T712 858-866 VBD denotes revealed
T713 867-871 IN denotes that
T714 898-906 VBD denotes resulted
T715 872-875 NN denotes K14
T716 876-879 NN denotes cre
T717 875-876 HYPH denotes -
T718 880-888 JJ denotes mediated
T719 879-880 HYPH denotes
T720 893-897 NN denotes loss
T721 889-892 NN denotes Apc
T722 907-909 IN denotes in
T723 910-918 JJ denotes aberrant
T724 919-925 NN denotes growth
T725 926-928 IN denotes in
T726 929-933 JJ denotes many
T727 964-973 NNS denotes epithelia
T728 934-946 RB denotes ectodermally
T729 947-954 VBN denotes derived
T730 955-963 JJ denotes squamous
T731 973-975 , denotes ,
T732 975-984 VBG denotes including
T733 985-989 NN denotes hair
T734 990-999 NNS denotes follicles
T735 999-1001 , denotes ,
T736 1001-1006 NNS denotes teeth
T737 1006-1008 , denotes ,
T738 1008-1011 CC denotes and
T739 1012-1016 JJ denotes oral
T740 1029-1038 NNS denotes epithelia
T741 1017-1020 CC denotes and
T742 1021-1028 JJ denotes corneal
T743 1038-1039 . denotes .
T744 1039-1146 sentence denotes In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus.
T745 1040-1042 IN denotes In
T746 1077-1085 VBN denotes observed
T747 1043-1051 NN denotes addition
T748 1051-1053 , denotes ,
T749 1053-1061 JJ denotes squamous
T750 1062-1072 NN denotes metaplasia
T751 1073-1076 VBD denotes was
T752 1086-1088 IN denotes in
T753 1089-1096 JJ denotes various
T754 1116-1123 NNS denotes tissues
T755 1097-1107 JJ denotes epithelial
T756 1108-1115 JJ denotes derived
T757 1107-1108 HYPH denotes -
T758 1123-1125 , denotes ,
T759 1125-1134 VBG denotes including
T760 1135-1138 DT denotes the
T761 1139-1145 NN denotes thymus
T762 1145-1146 . denotes .
T763 1146-1435 sentence denotes The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; ApcCKO/CKO mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial–mesenchymal interactions for their development.
T764 1147-1150 DT denotes The
T765 1160-1166 NN denotes growth
T766 1151-1159 JJ denotes aberrant
T767 1270-1277 VBP denotes suggest
T768 1167-1169 IN denotes of
T769 1170-1174 NN denotes hair
T770 1175-1184 NNS denotes follicles
T771 1185-1188 CC denotes and
T772 1189-1194 JJ denotes other
T773 1195-1205 NNS denotes appendages
T774 1206-1208 RB denotes as
T775 1214-1216 IN denotes as
T776 1209-1213 RB denotes well
T777 1217-1220 DT denotes the
T778 1228-1241 NNS denotes abnormalities
T779 1221-1227 JJ denotes thymic
T780 1242-1244 IN denotes in
T781 1245-1248 NN denotes K14
T782 1249-1252 NN denotes cre
T783 1248-1249 HYPH denotes -
T784 1265-1269 NNS denotes mice
T785 1252-1253 : denotes ;
T786 1254-1260 NN denotes ApcCKO
T787 1261-1264 NN denotes CKO
T788 1260-1261 HYPH denotes /
T789 1278-1281 DT denotes the
T790 1286-1290 NN denotes gene
T791 1282-1285 NN denotes Apc
T792 1291-1293 VBZ denotes is
T793 1294-1301 JJ denotes crucial
T794 1302-1304 IN denotes in
T795 1305-1314 JJ denotes embryonic
T796 1315-1320 NNS denotes cells
T797 1321-1323 TO denotes to
T798 1324-1331 VB denotes specify
T799 1332-1342 JJ denotes epithelial
T800 1343-1347 NN denotes cell
T801 1348-1353 NNS denotes fates
T802 1354-1356 IN denotes in
T803 1357-1363 NNS denotes organs
T804 1364-1368 WDT denotes that
T805 1369-1376 VBP denotes require
T806 1377-1387 JJ denotes epithelial
T807 1388-1399 JJ denotes mesenchymal
T808 1387-1388 HYPH denotes
T809 1400-1412 NNS denotes interactions
T810 1413-1416 IN denotes for
T811 1417-1422 PRP$ denotes their
T812 1423-1434 NN denotes development
T813 1434-1435 . denotes .
T2378 2845-2848 CC denotes and
T2364 2771-2782 JJ denotes Adenomatous
T2365 2793-2797 NN denotes coli
T2366 2783-2792 NN denotes polyposis
T2367 2804-2806 VBZ denotes is
T2368 2798-2799 -LRB- denotes (
T2369 2799-2802 NN denotes APC
T2370 2802-2803 -RRB- denotes )
T2371 2807-2808 DT denotes a
T2372 2809-2815 NN denotes member
T2373 2816-2818 IN denotes of
T2374 2819-2822 DT denotes the
T2375 2837-2844 NN denotes pathway
T2376 2823-2826 NN denotes Wnt
T2377 2827-2836 NN denotes signaling
T2379 2849-2852 CD denotes one
T2380 2876-2878 VBZ denotes is
T2381 2853-2855 IN denotes of
T2382 2856-2859 PRP$ denotes its
T2383 2866-2875 NNS denotes functions
T2384 2860-2865 JJ denotes known
T2385 2879-2881 TO denotes to
T2386 2882-2890 VB denotes regulate
T2387 2891-2894 DT denotes the
T2388 2895-2901 NNS denotes levels
T2389 2902-2904 IN denotes of
T2390 2905-2906 NN denotes β
T2391 2907-2914 NN denotes catenin
T2392 2906-2907 HYPH denotes -
T2393 2914-2915 . denotes .
T2394 2915-2988 sentence denotes Alterations in β-catenin regulation are very common in human tumors [1].
T2395 2916-2927 NNS denotes Alterations
T2396 2952-2955 VBP denotes are
T2397 2928-2930 IN denotes in
T2398 2931-2932 NN denotes β
T2399 2933-2940 NN denotes catenin
T2400 2932-2933 HYPH denotes -
T2401 2941-2951 NN denotes regulation
T2402 2956-2960 RB denotes very
T2403 2961-2967 JJ denotes common
T2404 2968-2970 IN denotes in
T2405 2971-2976 JJ denotes human
T2406 2977-2983 NNS denotes tumors
T2407 2984-2985 -LRB- denotes [
T2408 2985-2986 CD denotes 1
T2409 2986-2987 -RRB- denotes ]
T2410 2987-2988 . denotes .
T2411 2988-3177 sentence denotes Loss of APC is associated with stabilization of the cytosolic β-catenin that ultimately results in its migration to the nucleus and activating a cascade of events leading to tumorigenesis.
T2412 2989-2993 NN denotes Loss
T2413 3004-3014 VBN denotes associated
T2414 2994-2996 IN denotes of
T2415 2997-3000 NN denotes APC
T2416 3001-3003 VBZ denotes is
T2417 3015-3019 IN denotes with
T2418 3020-3033 NN denotes stabilization
T2419 3034-3036 IN denotes of
T2420 3037-3040 DT denotes the
T2421 3053-3060 NN denotes catenin
T2422 3041-3050 JJ denotes cytosolic
T2423 3051-3052 NN denotes β
T2424 3052-3053 HYPH denotes -
T2425 3061-3065 WDT denotes that
T2426 3077-3084 VBZ denotes results
T2427 3066-3076 RB denotes ultimately
T2428 3085-3087 IN denotes in
T2429 3088-3091 PRP$ denotes its
T2430 3092-3101 NN denotes migration
T2431 3102-3104 IN denotes to
T2432 3105-3108 DT denotes the
T2433 3109-3116 NN denotes nucleus
T2434 3117-3120 CC denotes and
T2435 3121-3131 VBG denotes activating
T2436 3132-3133 DT denotes a
T2437 3134-3141 NN denotes cascade
T2438 3142-3144 IN denotes of
T2439 3145-3151 NNS denotes events
T2440 3152-3159 VBG denotes leading
T2441 3160-3162 IN denotes to
T2442 3163-3176 NN denotes tumorigenesis
T2443 3176-3177 . denotes .
T2444 3177-3437 sentence denotes APC also interacts with a multitude of other cellular proteins, including axin-2 (AXIN2), plakoglobin (JUP), Asef (ARHGEF4), kinesin superfamily–associated protein 3 (KIFAP3), EB1 (MAPRE1), microtubules, and the human homolog of Drosophila discs large (DLG1).
T2445 3178-3181 NN denotes APC
T2446 3187-3196 VBZ denotes interacts
T2447 3182-3186 RB denotes also
T2448 3197-3201 IN denotes with
T2449 3202-3203 DT denotes a
T2450 3204-3213 NN denotes multitude
T2451 3214-3216 IN denotes of
T2452 3217-3222 JJ denotes other
T2453 3232-3240 NN denotes proteins
T2454 3223-3231 JJ denotes cellular
T2455 3240-3242 , denotes ,
T2456 3242-3251 VBG denotes including
T2457 3252-3256 NN denotes axin
T2458 3256-3257 HYPH denotes -
T2459 3257-3258 CD denotes 2
T2460 3259-3260 -LRB- denotes (
T2461 3260-3265 NN denotes AXIN2
T2462 3265-3266 -RRB- denotes )
T2463 3266-3268 , denotes ,
T2464 3268-3279 NN denotes plakoglobin
T2465 3280-3281 -LRB- denotes (
T2466 3281-3284 NN denotes JUP
T2467 3284-3285 -RRB- denotes )
T2468 3285-3287 , denotes ,
T2469 3287-3291 NN denotes Asef
T2470 3292-3293 -LRB- denotes (
T2471 3293-3300 NN denotes ARHGEF4
T2472 3300-3301 -RRB- denotes )
T2473 3301-3303 , denotes ,
T2474 3303-3310 NN denotes kinesin
T2475 3311-3322 NN denotes superfamily
T2476 3323-3333 VBN denotes associated
T2477 3322-3323 HYPH denotes
T2478 3334-3341 NN denotes protein
T2479 3342-3343 CD denotes 3
T2480 3344-3345 -LRB- denotes (
T2481 3345-3351 NN denotes KIFAP3
T2482 3351-3352 -RRB- denotes )
T2483 3352-3354 , denotes ,
T2484 3354-3357 NN denotes EB1
T2485 3358-3359 -LRB- denotes (
T2486 3359-3365 NN denotes MAPRE1
T2487 3365-3366 -RRB- denotes )
T2488 3366-3368 , denotes ,
T2489 3368-3380 NNS denotes microtubules
T2490 3380-3382 , denotes ,
T2491 3382-3385 CC denotes and
T2492 3386-3389 DT denotes the
T2493 3396-3403 NN denotes homolog
T2494 3390-3395 JJ denotes human
T2495 3404-3406 IN denotes of
T2496 3407-3417 NNP denotes Drosophila
T2497 3418-3423 NNS denotes discs
T2498 3424-3429 JJ denotes large
T2499 3430-3431 -LRB- denotes (
T2500 3431-3435 NN denotes DLG1
T2501 3435-3436 -RRB- denotes )
T2502 3436-3437 . denotes .
T2503 3437-3748 sentence denotes These interactions suggest that APC can potentially regulate many cellular functions, including intercellular adhesion, cytoskeletal organization, regulation of plakoglobin levels, regulation of the cell cycle and apoptosis, orientation of asymmetric stem cell division, and control of cell polarization [2,3].
T2504 3438-3443 DT denotes These
T2505 3444-3456 NNS denotes interactions
T2506 3457-3464 VBP denotes suggest
T2507 3465-3469 IN denotes that
T2508 3490-3498 VB denotes regulate
T2509 3470-3473 NN denotes APC
T2510 3474-3477 MD denotes can
T2511 3478-3489 RB denotes potentially
T2512 3499-3503 JJ denotes many
T2513 3513-3522 NNS denotes functions
T2514 3504-3512 JJ denotes cellular
T2515 3522-3524 , denotes ,
T2516 3524-3533 VBG denotes including
T2517 3534-3547 JJ denotes intercellular
T2518 3548-3556 NN denotes adhesion
T2519 3556-3558 , denotes ,
T2520 3558-3570 JJ denotes cytoskeletal
T2521 3571-3583 NN denotes organization
T2522 3583-3585 , denotes ,
T2523 3585-3595 NN denotes regulation
T2524 3596-3598 IN denotes of
T2525 3599-3610 NN denotes plakoglobin
T2526 3611-3617 NNS denotes levels
T2527 3617-3619 , denotes ,
T2528 3619-3629 NN denotes regulation
T2529 3630-3632 IN denotes of
T2530 3633-3636 DT denotes the
T2531 3642-3647 NN denotes cycle
T2532 3637-3641 NN denotes cell
T2533 3648-3651 CC denotes and
T2534 3652-3661 NN denotes apoptosis
T2535 3661-3663 , denotes ,
T2536 3663-3674 NN denotes orientation
T2537 3675-3677 IN denotes of
T2538 3678-3688 JJ denotes asymmetric
T2539 3699-3707 NN denotes division
T2540 3689-3693 NN denotes stem
T2541 3694-3698 NN denotes cell
T2542 3707-3709 , denotes ,
T2543 3709-3712 CC denotes and
T2544 3713-3720 NN denotes control
T2545 3721-3723 IN denotes of
T2546 3724-3728 NN denotes cell
T2547 3729-3741 NN denotes polarization
T2548 3742-3743 -LRB- denotes [
T2549 3745-3746 CD denotes 3
T2550 3743-3744 CD denotes 2
T2551 3744-3745 , denotes ,
T2552 3746-3747 -RRB- denotes ]
T2553 3747-3748 . denotes .
T2554 3748-3780 sentence denotes APC is a tumor suppressor gene.
T2555 3749-3752 NN denotes APC
T2556 3753-3755 VBZ denotes is
T2557 3756-3757 DT denotes a
T2558 3775-3779 NN denotes gene
T2559 3758-3763 NN denotes tumor
T2560 3764-3774 NN denotes suppressor
T2561 3779-3780 . denotes .
T2562 3780-3875 sentence denotes Somatic mutations in APC are frequently found in many sporadic tumors of the colon and rectum.
T2563 3781-3788 JJ denotes Somatic
T2564 3789-3798 NNS denotes mutations
T2565 3821-3826 VBN denotes found
T2566 3799-3801 IN denotes in
T2567 3802-3805 NN denotes APC
T2568 3806-3809 VBP denotes are
T2569 3810-3820 RB denotes frequently
T2570 3827-3829 IN denotes in
T2571 3830-3834 JJ denotes many
T2572 3844-3850 NNS denotes tumors
T2573 3835-3843 JJ denotes sporadic
T2574 3851-3853 IN denotes of
T2575 3854-3857 DT denotes the
T2576 3858-3863 NN denotes colon
T2577 3864-3867 CC denotes and
T2578 3868-3874 NN denotes rectum
T2579 3874-3875 . denotes .
T2580 3875-3997 sentence denotes Autosomal dominant germline mutations in APC cause familial adenomatous polypois (FAP) and its variant, Gardner syndrome.
T2581 3876-3885 JJ denotes Autosomal
T2582 3904-3913 NNS denotes mutations
T2583 3886-3894 JJ denotes dominant
T2584 3895-3903 NN denotes germline
T2585 3921-3926 VBP denotes cause
T2586 3914-3916 IN denotes in
T2587 3917-3920 NN denotes APC
T2588 3927-3935 JJ denotes familial
T2589 3948-3956 NN denotes polypois
T2590 3936-3947 JJ denotes adenomatous
T2591 3957-3958 -LRB- denotes (
T2592 3958-3961 NN denotes FAP
T2593 3961-3962 -RRB- denotes )
T2594 3963-3966 CC denotes and
T2595 3967-3970 PRP$ denotes its
T2596 3971-3978 NN denotes variant
T2597 3978-3980 , denotes ,
T2598 3980-3987 NNP denotes Gardner
T2599 3988-3996 NN denotes syndrome
T2600 3996-3997 . denotes .
T2601 3997-4180 sentence denotes FAP patients are characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer in the third and fourth decades of life [4,5].
T2602 3998-4001 NN denotes FAP
T2603 4002-4010 NNS denotes patients
T2604 4015-4028 VBN denotes characterized
T2605 4011-4014 VBP denotes are
T2606 4029-4031 IN denotes by
T2607 4032-4040 NNS denotes hundreds
T2608 4041-4043 IN denotes of
T2609 4044-4055 JJ denotes adenomatous
T2610 4067-4073 NNS denotes polyps
T2611 4056-4066 JJ denotes colorectal
T2612 4073-4075 , denotes ,
T2613 4075-4079 IN denotes with
T2614 4080-4082 DT denotes an
T2615 4101-4112 NN denotes progression
T2616 4083-4089 RB denotes almost
T2617 4090-4100 JJ denotes inevitable
T2618 4113-4115 IN denotes to
T2619 4116-4126 JJ denotes colorectal
T2620 4127-4133 NN denotes cancer
T2621 4134-4136 IN denotes in
T2622 4137-4140 DT denotes the
T2623 4158-4165 NNS denotes decades
T2624 4141-4146 JJ denotes third
T2625 4147-4150 CC denotes and
T2626 4151-4157 JJ denotes fourth
T2627 4166-4168 IN denotes of
T2628 4169-4173 NN denotes life
T2629 4174-4175 -LRB- denotes [
T2630 4177-4178 CD denotes 5
T2631 4175-4176 CD denotes 4
T2632 4176-4177 , denotes ,
T2633 4178-4179 -RRB- denotes ]
T2634 4179-4180 . denotes .
T2635 4180-4545 sentence denotes In addition to colorectal neoplams, these individuals can develop extracolonic symptoms, among which are upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, disorders of the maxillary and skeletal bones, and dental abnormalities [6], suggesting the importance of APC gene functions in these organ systems.
T2636 4181-4183 IN denotes In
T2637 4239-4246 VB denotes develop
T2638 4184-4192 NN denotes addition
T2639 4193-4195 IN denotes to
T2640 4196-4206 JJ denotes colorectal
T2641 4207-4215 NNS denotes neoplams
T2642 4215-4217 , denotes ,
T2643 4217-4222 DT denotes these
T2644 4223-4234 NNS denotes individuals
T2645 4235-4238 MD denotes can
T2646 4247-4259 JJ denotes extracolonic
T2647 4260-4268 NNS denotes symptoms
T2648 4268-4270 , denotes ,
T2649 4270-4275 IN denotes among
T2650 4282-4285 VBP denotes are
T2651 4276-4281 WDT denotes which
T2652 4286-4291 JJ denotes upper
T2653 4309-4314 NN denotes tract
T2654 4292-4308 JJ denotes gastrointestinal
T2655 4315-4321 NNS denotes polyps
T2656 4321-4323 , denotes ,
T2657 4323-4333 JJ denotes congenital
T2658 4334-4345 NN denotes hypertrophy
T2659 4346-4348 IN denotes of
T2660 4349-4352 DT denotes the
T2661 4369-4379 NN denotes epithelium
T2662 4353-4360 JJ denotes retinal
T2663 4361-4368 NN denotes pigment
T2664 4379-4381 , denotes ,
T2665 4381-4388 JJ denotes desmoid
T2666 4389-4395 NNS denotes tumors
T2667 4395-4397 , denotes ,
T2668 4397-4406 NNS denotes disorders
T2669 4407-4409 IN denotes of
T2670 4410-4413 DT denotes the
T2671 4437-4442 NNS denotes bones
T2672 4414-4423 JJ denotes maxillary
T2673 4424-4427 CC denotes and
T2674 4428-4436 JJ denotes skeletal
T2675 4442-4444 , denotes ,
T2676 4444-4447 CC denotes and
T2677 4448-4454 JJ denotes dental
T2678 4455-4468 NNS denotes abnormalities
T2679 4469-4470 -LRB- denotes [
T2680 4470-4471 CD denotes 6
T2681 4471-4472 -RRB- denotes ]
T2682 4472-4474 , denotes ,
T2683 4474-4484 VBG denotes suggesting
T2684 4485-4488 DT denotes the
T2685 4489-4499 NN denotes importance
T2686 4500-4502 IN denotes of
T2687 4503-4506 NN denotes APC
T2688 4507-4511 NN denotes gene
T2689 4512-4521 VBZ denotes functions
T2690 4522-4524 IN denotes in
T2691 4525-4530 DT denotes these
T2692 4537-4544 NNS denotes systems
T2693 4531-4536 NN denotes organ
T2694 4544-4545 . denotes .
T2695 4545-4714 sentence denotes Although the role of APC in the initiation of human colorectal cancer is well established, its role in other tissue and developmental processes are not well understood.
T2696 4546-4554 IN denotes Although
T2697 4616-4618 VBZ denotes is
T2698 4555-4558 DT denotes the
T2699 4559-4563 NN denotes role
T2700 4564-4566 IN denotes of
T2701 4567-4570 NN denotes APC
T2702 4571-4573 IN denotes in
T2703 4574-4577 DT denotes the
T2704 4578-4588 NN denotes initiation
T2705 4589-4591 IN denotes of
T2706 4592-4597 JJ denotes human
T2707 4609-4615 NN denotes cancer
T2708 4598-4608 JJ denotes colorectal
T2709 4703-4713 VBN denotes understood
T2710 4619-4623 RB denotes well
T2711 4624-4635 JJ denotes established
T2712 4635-4637 , denotes ,
T2713 4637-4640 PRP$ denotes its
T2714 4641-4645 NN denotes role
T2715 4646-4648 IN denotes in
T2716 4649-4654 JJ denotes other
T2717 4680-4689 NNS denotes processes
T2718 4655-4661 NN denotes tissue
T2719 4662-4665 CC denotes and
T2720 4666-4679 JJ denotes developmental
T2721 4690-4693 VBP denotes are
T2722 4694-4697 RB denotes not
T2723 4698-4702 RB denotes well
T2724 4713-4714 . denotes .
T2725 4714-4977 sentence denotes Given the importance of regulation of Wnt signaling in embryonic pattern formation and morphogenesis of many organs, mechanistic understanding of APC in development and in extracolonic tissues becomes critical to better assess potential adverse events in humans.
T2726 4715-4720 VBN denotes Given
T2727 4908-4915 VBZ denotes becomes
T2728 4721-4724 DT denotes the
T2729 4725-4735 NN denotes importance
T2730 4736-4738 IN denotes of
T2731 4739-4749 NN denotes regulation
T2732 4750-4752 IN denotes of
T2733 4753-4756 NN denotes Wnt
T2734 4757-4766 NN denotes signaling
T2735 4767-4769 IN denotes in
T2736 4770-4779 JJ denotes embryonic
T2737 4788-4797 NN denotes formation
T2738 4780-4787 NN denotes pattern
T2739 4798-4801 CC denotes and
T2740 4802-4815 NN denotes morphogenesis
T2741 4816-4818 IN denotes of
T2742 4819-4823 JJ denotes many
T2743 4824-4830 NNS denotes organs
T2744 4830-4832 , denotes ,
T2745 4832-4843 JJ denotes mechanistic
T2746 4844-4857 NN denotes understanding
T2747 4858-4860 IN denotes of
T2748 4861-4864 NN denotes APC
T2749 4865-4867 IN denotes in
T2750 4868-4879 NN denotes development
T2751 4880-4883 CC denotes and
T2752 4884-4886 IN denotes in
T2753 4887-4899 JJ denotes extracolonic
T2754 4900-4907 NNS denotes tissues
T2755 4916-4924 JJ denotes critical
T2756 4925-4927 TO denotes to
T2757 4935-4941 VB denotes assess
T2758 4928-4934 RBR denotes better
T2759 4942-4951 JJ denotes potential
T2760 4960-4966 NNS denotes events
T2761 4952-4959 JJ denotes adverse
T2762 4967-4969 IN denotes in
T2763 4970-4976 NNS denotes humans
T2764 4976-4977 . denotes .
T2765 4977-5089 sentence denotes One approach to understand the role of Apc in development is to develop mice with an inactivating Apc mutation.
T2766 4978-4981 CD denotes One
T2767 4982-4990 NN denotes approach
T2768 5036-5038 VBZ denotes is
T2769 4991-4993 TO denotes to
T2770 4994-5004 VB denotes understand
T2771 5005-5008 DT denotes the
T2772 5009-5013 NN denotes role
T2773 5014-5016 IN denotes of
T2774 5017-5020 NN denotes Apc
T2775 5021-5023 IN denotes in
T2776 5024-5035 NN denotes development
T2777 5039-5041 TO denotes to
T2778 5042-5049 VB denotes develop
T2779 5050-5054 NNS denotes mice
T2780 5055-5059 IN denotes with
T2781 5060-5062 DT denotes an
T2782 5080-5088 NN denotes mutation
T2783 5063-5075 VBG denotes inactivating
T2784 5076-5079 NN denotes Apc
T2785 5088-5089 . denotes .
T2786 5089-5168 sentence denotes Several genetically modified mouse strains for Apc have been described [7–10].
T2787 5090-5097 JJ denotes Several
T2788 5125-5132 NNS denotes strains
T2789 5098-5109 RB denotes genetically
T2790 5110-5118 VBN denotes modified
T2791 5119-5124 NN denotes mouse
T2792 5151-5160 VBN denotes described
T2793 5133-5136 IN denotes for
T2794 5137-5140 NN denotes Apc
T2795 5141-5145 VBP denotes have
T2796 5146-5150 VBN denotes been
T2797 5161-5162 -LRB- denotes [
T2798 5162-5163 CD denotes 7
T2799 5163-5164 SYM denotes
T2800 5164-5166 CD denotes 10
T2801 5166-5167 -RRB- denotes ]
T2802 5167-5168 . denotes .
T2803 5168-5290 sentence denotes Most of these models, in the heterozygous state, show a gastrointestinal and other tumor predisposition phenotype [7–10].
T2804 5169-5173 JJS denotes Most
T2805 5218-5222 VBP denotes show
T2806 5174-5176 IN denotes of
T2807 5177-5182 DT denotes these
T2808 5183-5189 NNS denotes models
T2809 5189-5191 , denotes ,
T2810 5191-5193 IN denotes in
T2811 5194-5197 DT denotes the
T2812 5211-5216 NN denotes state
T2813 5198-5210 JJ denotes heterozygous
T2814 5216-5218 , denotes ,
T2815 5223-5224 DT denotes a
T2816 5273-5282 NN denotes phenotype
T2817 5225-5241 JJ denotes gastrointestinal
T2818 5252-5257 NN denotes tumor
T2819 5242-5245 CC denotes and
T2820 5246-5251 JJ denotes other
T2821 5258-5272 NN denotes predisposition
T2822 5283-5284 -LRB- denotes [
T2823 5284-5285 CD denotes 7
T2824 5285-5286 SYM denotes
T2825 5286-5288 CD denotes 10
T2826 5288-5289 -RRB- denotes ]
T2827 5289-5290 . denotes .
T2828 5290-5445 sentence denotes Mouse embryos that are homozygous for the genetic modification die during embryogenesis, and some of the models do not survive beyond gastrulation [8,11].
T2829 5291-5296 NN denotes Mouse
T2830 5297-5304 NNS denotes embryos
T2831 5354-5357 VBP denotes die
T2832 5305-5309 WDT denotes that
T2833 5310-5313 VBP denotes are
T2834 5314-5324 JJ denotes homozygous
T2835 5325-5328 IN denotes for
T2836 5329-5332 DT denotes the
T2837 5341-5353 NN denotes modification
T2838 5333-5340 JJ denotes genetic
T2839 5358-5364 IN denotes during
T2840 5365-5378 NN denotes embryogenesis
T2841 5378-5380 , denotes ,
T2842 5380-5383 CC denotes and
T2843 5384-5388 DT denotes some
T2844 5410-5417 VB denotes survive
T2845 5389-5391 IN denotes of
T2846 5392-5395 DT denotes the
T2847 5396-5402 NNS denotes models
T2848 5403-5405 VBP denotes do
T2849 5406-5409 RB denotes not
T2850 5418-5424 IN denotes beyond
T2851 5425-5437 NN denotes gastrulation
T2852 5438-5439 -LRB- denotes [
T2853 5441-5443 CD denotes 11
T2854 5439-5440 CD denotes 8
T2855 5440-5441 , denotes ,
T2856 5443-5444 -RRB- denotes ]
T2857 5444-5445 . denotes .
T2858 5445-5733 sentence denotes An alternate approach to understand the role of Apc in development and/or in specific tissues is to generate a mouse strain that carries a conditionally modified allele and mate it with a mouse strain that facilitates the modification of the conditional allele in specific cell lineages.
T2859 5446-5448 DT denotes An
T2860 5459-5467 NN denotes approach
T2861 5449-5458 JJ denotes alternate
T2862 5540-5542 VBZ denotes is
T2863 5468-5470 TO denotes to
T2864 5471-5481 VB denotes understand
T2865 5482-5485 DT denotes the
T2866 5486-5490 NN denotes role
T2867 5491-5493 IN denotes of
T2868 5494-5497 NN denotes Apc
T2869 5498-5500 IN denotes in
T2870 5501-5512 NN denotes development
T2871 5513-5516 CC denotes and
T2872 5516-5517 HYPH denotes /
T2873 5517-5519 CC denotes or
T2874 5520-5522 IN denotes in
T2875 5523-5531 JJ denotes specific
T2876 5532-5539 NNS denotes tissues
T2877 5543-5545 TO denotes to
T2878 5546-5554 VB denotes generate
T2879 5555-5556 DT denotes a
T2880 5563-5569 NN denotes strain
T2881 5557-5562 NN denotes mouse
T2882 5570-5574 WDT denotes that
T2883 5575-5582 VBZ denotes carries
T2884 5583-5584 DT denotes a
T2885 5608-5614 NN denotes allele
T2886 5585-5598 RB denotes conditionally
T2887 5599-5607 VBN denotes modified
T2888 5615-5618 CC denotes and
T2889 5619-5623 VB denotes mate
T2890 5624-5626 PRP denotes it
T2891 5627-5631 IN denotes with
T2892 5632-5633 DT denotes a
T2893 5640-5646 NN denotes strain
T2894 5634-5639 NN denotes mouse
T2895 5647-5651 WDT denotes that
T2896 5652-5663 VBZ denotes facilitates
T2897 5664-5667 DT denotes the
T2898 5668-5680 NN denotes modification
T2899 5681-5683 IN denotes of
T2900 5684-5687 DT denotes the
T2901 5700-5706 NN denotes allele
T2902 5688-5699 JJ denotes conditional
T2903 5707-5709 IN denotes in
T2904 5710-5718 JJ denotes specific
T2905 5724-5732 NNS denotes lineages
T2906 5719-5723 NN denotes cell
T2907 5732-5733 . denotes .
T2908 5733-5892 sentence denotes To assess the role of Apc in different stages of life systematically, we generated mice containing a conditional knockout (CKO) mutant allele of Apc (ApcCKO).
T2909 5734-5736 TO denotes To
T2910 5737-5743 VB denotes assess
T2911 5807-5816 VBD denotes generated
T2912 5744-5747 DT denotes the
T2913 5748-5752 NN denotes role
T2914 5753-5755 IN denotes of
T2915 5756-5759 NN denotes Apc
T2916 5760-5762 IN denotes in
T2917 5763-5772 JJ denotes different
T2918 5773-5779 NNS denotes stages
T2919 5780-5782 IN denotes of
T2920 5783-5787 NN denotes life
T2921 5788-5802 RB denotes systematically
T2922 5802-5804 , denotes ,
T2923 5804-5806 PRP denotes we
T2924 5817-5821 NNS denotes mice
T2925 5822-5832 VBG denotes containing
T2926 5833-5834 DT denotes a
T2927 5869-5875 NN denotes allele
T2928 5835-5846 JJ denotes conditional
T2929 5847-5855 NN denotes knockout
T2930 5856-5857 -LRB- denotes (
T2931 5857-5860 NN denotes CKO
T2932 5860-5861 -RRB- denotes )
T2933 5862-5868 JJ denotes mutant
T2934 5876-5878 IN denotes of
T2935 5879-5882 NN denotes Apc
T2936 5883-5884 -LRB- denotes (
T2937 5884-5890 NN denotes ApcCKO
T2938 5890-5891 -RRB- denotes )
T2939 5891-5892 . denotes .
T2940 5892-6087 sentence denotes These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia.
T2941 5893-5898 DT denotes These
T2942 5899-5903 NNS denotes mice
T2943 5909-5914 VBN denotes mated
T2944 5904-5908 VBD denotes were
T2945 5915-5919 IN denotes with
T2946 5920-5921 DT denotes a
T2947 5922-5928 NN denotes strain
T2948 5929-5937 VBG denotes carrying
T2949 5938-5941 NN denotes Cre
T2950 5942-5953 NN denotes recombinase
T2951 5954-5959 IN denotes under
T2952 5960-5963 DT denotes the
T2953 5964-5971 NN denotes control
T2954 5972-5974 IN denotes of
T2955 5975-5978 DT denotes the
T2956 6002-6010 NN denotes promoter
T2957 5979-5984 JJ denotes human
T2958 5985-5992 NN denotes Keratin
T2959 5993-5995 CD denotes 14
T2960 5996-5997 -LRB- denotes (
T2961 5997-6000 NN denotes K14
T2962 6000-6001 -RRB- denotes )
T2963 6010-6012 , denotes ,
T2964 6012-6017 WDT denotes which
T2965 6018-6020 VBZ denotes is
T2966 6021-6027 JJ denotes active
T2967 6028-6030 IN denotes in
T2968 6031-6036 JJ denotes basal
T2969 6037-6042 NNS denotes cells
T2970 6043-6045 IN denotes of
T2971 6046-6055 NN denotes epidermis
T2972 6056-6059 CC denotes and
T2973 6060-6065 JJ denotes other
T2974 6077-6086 NNS denotes epithelia
T2975 6066-6076 JJ denotes stratified
T2976 6086-6087 . denotes .
T2977 6087-6334 sentence denotes We report here that K14 promoter-driven loss of Apc resulted in aberrant development of several organs that require inductive epithelial–mesenchymal interactions, including hair follicle, teeth, and thymus, and resulted in neonatal death in mice.
T2978 6088-6090 PRP denotes We
T2979 6091-6097 VBP denotes report
T2980 6098-6102 RB denotes here
T2981 6103-6107 IN denotes that
T2982 6140-6148 VBD denotes resulted
T2983 6108-6111 NN denotes K14
T2984 6112-6120 NN denotes promoter
T2985 6121-6127 VBN denotes driven
T2986 6120-6121 HYPH denotes -
T2987 6128-6132 NN denotes loss
T2988 6133-6135 IN denotes of
T2989 6136-6139 NN denotes Apc
T2990 6149-6151 IN denotes in
T2991 6152-6160 JJ denotes aberrant
T2992 6161-6172 NN denotes development
T2993 6173-6175 IN denotes of
T2994 6176-6183 JJ denotes several
T2995 6184-6190 NNS denotes organs
T2996 6191-6195 WDT denotes that
T2997 6196-6203 VBP denotes require
T2998 6204-6213 JJ denotes inductive
T2999 6237-6249 NNS denotes interactions
T3000 6214-6224 JJ denotes epithelial
T3001 6225-6236 JJ denotes mesenchymal
T3002 6224-6225 HYPH denotes
T3003 6249-6251 , denotes ,
T3004 6251-6260 VBG denotes including
T3005 6261-6265 NN denotes hair
T3006 6266-6274 NN denotes follicle
T3007 6274-6276 , denotes ,
T3008 6276-6281 NNS denotes teeth
T3009 6281-6283 , denotes ,
T3010 6283-6286 CC denotes and
T3011 6287-6293 NN denotes thymus
T3012 6293-6295 , denotes ,
T3013 6295-6298 CC denotes and
T3014 6299-6307 VBD denotes resulted
T3015 6308-6310 IN denotes in
T3016 6311-6319 JJ denotes neonatal
T3017 6320-6325 NN denotes death
T3018 6326-6328 IN denotes in
T3019 6329-6333 NNS denotes mice
T3020 6333-6334 . denotes .
T3021 6334-6560 sentence denotes We found that Apc plays a crucial role in determinations of cell fates during the embryonic development, possibly via temporal and tissue-specific regulation of β-catenin levels in the skin, its appendages, and in the thymus.
T3022 6335-6337 PRP denotes We
T3023 6338-6343 VBD denotes found
T3024 6344-6348 IN denotes that
T3025 6353-6358 VBZ denotes plays
T3026 6349-6352 NN denotes Apc
T3027 6359-6360 DT denotes a
T3028 6369-6373 NN denotes role
T3029 6361-6368 JJ denotes crucial
T3030 6374-6376 IN denotes in
T3031 6377-6391 NNS denotes determinations
T3032 6392-6394 IN denotes of
T3033 6395-6399 NN denotes cell
T3034 6400-6405 NNS denotes fates
T3035 6406-6412 IN denotes during
T3036 6413-6416 DT denotes the
T3037 6427-6438 NN denotes development
T3038 6417-6426 JJ denotes embryonic
T3039 6438-6440 , denotes ,
T3040 6440-6448 RB denotes possibly
T3041 6449-6452 IN denotes via
T3042 6453-6461 JJ denotes temporal
T3043 6482-6492 NN denotes regulation
T3044 6462-6465 CC denotes and
T3045 6466-6472 NN denotes tissue
T3046 6473-6481 JJ denotes specific
T3047 6472-6473 HYPH denotes -
T3048 6493-6495 IN denotes of
T3049 6496-6497 NN denotes β
T3050 6498-6505 NN denotes catenin
T3051 6497-6498 HYPH denotes -
T3052 6506-6512 NNS denotes levels
T3053 6513-6515 IN denotes in
T3054 6516-6519 DT denotes the
T3055 6520-6524 NN denotes skin
T3056 6524-6526 , denotes ,
T3057 6526-6529 PRP$ denotes its
T3058 6530-6540 NNS denotes appendages
T3059 6540-6542 , denotes ,
T3060 6542-6545 CC denotes and
T3061 6546-6548 IN denotes in
T3062 6549-6552 DT denotes the
T3063 6553-6559 NN denotes thymus
T3064 6559-6560 . denotes .
T4597 6571-6581 NN denotes Generation
T4598 6582-6584 IN denotes of
T4599 6585-6588 DT denotes the
T4600 6608-6612 NNS denotes Mice
T4601 6589-6595 NN denotes ApcCKO
T4602 6596-6599 CC denotes and
T4603 6600-6607 NN denotes ApcΔ580
T4604 6612-6779 sentence denotes To investigate the role of Apc in development of skin and its appendages, we used the Cre/loxP technology to introduce a conditional mutation of the Apc gene in mice.
T4605 6613-6615 TO denotes To
T4606 6616-6627 VB denotes investigate
T4607 6690-6694 VBD denotes used
T4608 6628-6631 DT denotes the
T4609 6632-6636 NN denotes role
T4610 6637-6639 IN denotes of
T4611 6640-6643 NN denotes Apc
T4612 6644-6646 IN denotes in
T4613 6647-6658 NN denotes development
T4614 6659-6661 IN denotes of
T4615 6662-6666 NN denotes skin
T4616 6667-6670 CC denotes and
T4617 6671-6674 PRP$ denotes its
T4618 6675-6685 NNS denotes appendages
T4619 6685-6687 , denotes ,
T4620 6687-6689 PRP denotes we
T4621 6695-6698 DT denotes the
T4622 6708-6718 NN denotes technology
T4623 6699-6702 NN denotes Cre
T4624 6703-6707 NN denotes loxP
T4625 6702-6703 HYPH denotes /
T4626 6719-6721 TO denotes to
T4627 6722-6731 VB denotes introduce
T4628 6732-6733 DT denotes a
T4629 6746-6754 NN denotes mutation
T4630 6734-6745 JJ denotes conditional
T4631 6755-6757 IN denotes of
T4632 6758-6761 DT denotes the
T4633 6766-6770 NN denotes gene
T4634 6762-6765 NN denotes Apc
T4635 6771-6773 IN denotes in
T4636 6774-6778 NNS denotes mice
T4637 6778-6779 . denotes .
T4638 6779-7079 sentence denotes We constructed embryonic stem (ES) cells and mice carrying an Apc allele harboring both a pair of loxP sites flanking Apc exon 14 and a pair of FLP recognition target (FRT) sites flanking PGK-neomycin selection cassette by recombineering [12,13] (Figure 1A, ApcCKON allele, N for neomycin cassette).
T4639 6780-6782 PRP denotes We
T4640 6783-6794 VBD denotes constructed
T4641 6795-6804 JJ denotes embryonic
T4642 6805-6809 NN denotes stem
T4643 6815-6820 NNS denotes cells
T4644 6810-6811 -LRB- denotes (
T4645 6811-6813 NN denotes ES
T4646 6813-6814 -RRB- denotes )
T4647 6821-6824 CC denotes and
T4648 6825-6829 NNS denotes mice
T4649 6830-6838 VBG denotes carrying
T4650 6839-6841 DT denotes an
T4651 6846-6852 NN denotes allele
T4652 6842-6845 NN denotes Apc
T4653 6853-6862 VBG denotes harboring
T4654 6863-6867 CC denotes both
T4655 6870-6874 NN denotes pair
T4656 6868-6869 DT denotes a
T4657 6875-6877 IN denotes of
T4658 6878-6882 NN denotes loxP
T4659 6883-6888 NNS denotes sites
T4660 6889-6897 VBG denotes flanking
T4661 6898-6901 NN denotes Apc
T4662 6902-6906 NN denotes exon
T4663 6907-6909 CD denotes 14
T4664 6910-6913 CC denotes and
T4665 6914-6915 DT denotes a
T4666 6916-6920 NN denotes pair
T4667 6921-6923 IN denotes of
T4668 6924-6927 NN denotes FLP
T4669 6940-6946 NN denotes target
T4670 6928-6939 NN denotes recognition
T4671 6953-6958 NNS denotes sites
T4672 6947-6948 -LRB- denotes (
T4673 6948-6951 NN denotes FRT
T4674 6951-6952 -RRB- denotes )
T4675 6959-6967 VBG denotes flanking
T4676 6968-6971 NN denotes PGK
T4677 6972-6980 NN denotes neomycin
T4678 6971-6972 HYPH denotes -
T4679 6991-6999 NN denotes cassette
T4680 6981-6990 NN denotes selection
T4681 7000-7002 IN denotes by
T4682 7003-7017 VBG denotes recombineering
T4683 7018-7019 -LRB- denotes [
T4684 7022-7024 CD denotes 13
T4685 7019-7021 CD denotes 12
T4686 7021-7022 , denotes ,
T4687 7024-7025 -RRB- denotes ]
T4688 7026-7027 -LRB- denotes (
T4689 7054-7055 NN denotes N
T4690 7027-7033 NN denotes Figure
T4691 7034-7036 NN denotes 1A
T4692 7036-7038 , denotes ,
T4693 7038-7045 NN denotes ApcCKON
T4694 7046-7052 NN denotes allele
T4695 7052-7054 , denotes ,
T4696 7056-7059 IN denotes for
T4697 7060-7068 NN denotes neomycin
T4698 7069-7077 NN denotes cassette
T4699 7077-7078 -RRB- denotes )
T4700 7078-7079 . denotes .
T4701 7079-7200 sentence denotes A PGK-neomycin cassette was inserted in the same transcriptional orientation as Apc in intron 14 of the endogenous gene.
T4702 7080-7081 DT denotes A
T4703 7095-7103 NN denotes cassette
T4704 7082-7085 NN denotes PGK
T4705 7086-7094 NN denotes neomycin
T4706 7085-7086 HYPH denotes -
T4707 7108-7116 VBN denotes inserted
T4708 7104-7107 VBD denotes was
T4709 7117-7119 IN denotes in
T4710 7120-7123 DT denotes the
T4711 7145-7156 NN denotes orientation
T4712 7124-7128 JJ denotes same
T4713 7129-7144 JJ denotes transcriptional
T4714 7157-7159 IN denotes as
T4715 7160-7163 NN denotes Apc
T4716 7164-7166 IN denotes in
T4717 7167-7173 NN denotes intron
T4718 7174-7176 CD denotes 14
T4719 7177-7179 IN denotes of
T4720 7180-7183 DT denotes the
T4721 7195-7199 NN denotes gene
T4722 7184-7194 JJ denotes endogenous
T4723 7199-7200 . denotes .
T4724 7200-7278 sentence denotes The loxP and FRT sites were used to aid unidirectional recombination [12,13].
T4725 7201-7204 DT denotes The
T4726 7218-7223 NNS denotes sites
T4727 7205-7209 NN denotes loxP
T4728 7210-7213 CC denotes and
T4729 7214-7217 NN denotes FRT
T4730 7229-7233 VBN denotes used
T4731 7224-7228 VBD denotes were
T4732 7234-7236 TO denotes to
T4733 7237-7240 VB denotes aid
T4734 7241-7255 JJ denotes unidirectional
T4735 7256-7269 NN denotes recombination
T4736 7270-7271 -LRB- denotes [
T4737 7274-7276 CD denotes 13
T4738 7271-7273 CD denotes 12
T4739 7273-7274 , denotes ,
T4740 7276-7277 -RRB- denotes ]
T4741 7277-7278 . denotes .
T4742 7278-7428 sentence denotes Two mouse lines containing the same modification were generated from two independent ES clones to ensure that these two lines behave in the same way.
T4743 7279-7282 CD denotes Two
T4744 7289-7294 NNS denotes lines
T4745 7283-7288 NN denotes mouse
T4746 7333-7342 VBN denotes generated
T4747 7295-7305 VBG denotes containing
T4748 7306-7309 DT denotes the
T4749 7315-7327 NN denotes modification
T4750 7310-7314 JJ denotes same
T4751 7328-7332 VBD denotes were
T4752 7343-7347 IN denotes from
T4753 7348-7351 CD denotes two
T4754 7367-7373 NNS denotes clones
T4755 7352-7363 JJ denotes independent
T4756 7364-7366 NN denotes ES
T4757 7374-7376 TO denotes to
T4758 7377-7383 VB denotes ensure
T4759 7384-7388 IN denotes that
T4760 7405-7411 VBP denotes behave
T4761 7389-7394 DT denotes these
T4762 7399-7404 NNS denotes lines
T4763 7395-7398 CD denotes two
T4764 7412-7414 IN denotes in
T4765 7415-7418 DT denotes the
T4766 7424-7427 NN denotes way
T4767 7419-7423 JJ denotes same
T4768 7427-7428 . denotes .
T4769 7428-7680 sentence denotes These ApcCKON/+ mice were crossed with FLPe-deleter to generate ApcCKO/+ mice that were heterozygous for the final Apc conditional (ApcCKO) allele that removed the PGK-neomycin cassette and contains only the loxP sites in the introns flanking exon 14.
T4770 7429-7434 DT denotes These
T4771 7445-7449 NNS denotes mice
T4772 7435-7442 NN denotes ApcCKON
T4773 7442-7443 HYPH denotes /
T4774 7443-7444 SYM denotes +
T4775 7455-7462 VBN denotes crossed
T4776 7450-7454 VBD denotes were
T4777 7463-7467 IN denotes with
T4778 7468-7472 NN denotes FLPe
T4779 7473-7480 NN denotes deleter
T4780 7472-7473 HYPH denotes -
T4781 7481-7483 TO denotes to
T4782 7484-7492 VB denotes generate
T4783 7493-7499 NN denotes ApcCKO
T4784 7502-7506 NNS denotes mice
T4785 7499-7500 HYPH denotes /
T4786 7500-7501 SYM denotes +
T4787 7507-7511 WDT denotes that
T4788 7512-7516 VBD denotes were
T4789 7517-7529 JJ denotes heterozygous
T4790 7530-7533 IN denotes for
T4791 7534-7537 DT denotes the
T4792 7569-7575 NN denotes allele
T4793 7538-7543 JJ denotes final
T4794 7544-7547 NN denotes Apc
T4795 7548-7559 JJ denotes conditional
T4796 7560-7561 -LRB- denotes (
T4797 7561-7567 NN denotes ApcCKO
T4798 7567-7568 -RRB- denotes )
T4799 7576-7580 WDT denotes that
T4800 7581-7588 VBD denotes removed
T4801 7589-7592 DT denotes the
T4802 7606-7614 NN denotes cassette
T4803 7593-7596 NN denotes PGK
T4804 7597-7605 NN denotes neomycin
T4805 7596-7597 HYPH denotes -
T4806 7615-7618 CC denotes and
T4807 7619-7627 VBZ denotes contains
T4808 7628-7632 RB denotes only
T4809 7642-7647 NNS denotes sites
T4810 7633-7636 DT denotes the
T4811 7637-7641 NN denotes loxP
T4812 7648-7650 IN denotes in
T4813 7651-7654 DT denotes the
T4814 7655-7662 NNS denotes introns
T4815 7663-7671 VBG denotes flanking
T4816 7672-7676 NN denotes exon
T4817 7677-7679 CD denotes 14
T4818 7679-7680 . denotes .
T4819 7680-7861 sentence denotes To assess the effect of deleting exon 14 in mice, both lines of ApcCKO/+ mice were crossed with the Cre-deleter to generate the germline knockout line of Apc, designated ApcΔ580/+.
T4820 7681-7683 TO denotes To
T4821 7684-7690 VB denotes assess
T4822 7764-7771 VBN denotes crossed
T4823 7691-7694 DT denotes the
T4824 7695-7701 NN denotes effect
T4825 7702-7704 IN denotes of
T4826 7705-7713 VBG denotes deleting
T4827 7714-7718 NN denotes exon
T4828 7719-7721 CD denotes 14
T4829 7722-7724 IN denotes in
T4830 7725-7729 NNS denotes mice
T4831 7729-7731 , denotes ,
T4832 7731-7735 DT denotes both
T4833 7736-7741 NNS denotes lines
T4834 7742-7744 IN denotes of
T4835 7745-7751 NN denotes ApcCKO
T4836 7754-7758 NNS denotes mice
T4837 7751-7752 HYPH denotes /
T4838 7752-7753 SYM denotes +
T4839 7759-7763 VBD denotes were
T4840 7772-7776 IN denotes with
T4841 7777-7780 DT denotes the
T4842 7785-7792 NN denotes deleter
T4843 7781-7784 NN denotes Cre
T4844 7784-7785 HYPH denotes -
T4845 7793-7795 TO denotes to
T4846 7796-7804 VB denotes generate
T4847 7805-7808 DT denotes the
T4848 7827-7831 NN denotes line
T4849 7809-7817 NN denotes germline
T4850 7818-7826 NN denotes knockout
T4851 7832-7834 IN denotes of
T4852 7835-7838 NNP denotes Apc
T4853 7838-7840 , denotes ,
T4854 7840-7850 VBN denotes designated
T4855 7851-7858 NN denotes ApcΔ580
T4856 7858-7859 HYPH denotes /
T4857 7859-7860 SYM denotes +
T4858 7860-7861 . denotes .
T4859 7861-7916 sentence denotes The mutant allele (ApcΔ580) lacks exon 14 (Figure 1A).
T4860 7862-7865 DT denotes The
T4861 7873-7879 NN denotes allele
T4862 7866-7872 JJ denotes mutant
T4863 7890-7895 VBZ denotes lacks
T4864 7880-7881 -LRB- denotes (
T4865 7881-7888 NN denotes ApcΔ580
T4866 7888-7889 -RRB- denotes )
T4867 7896-7900 NN denotes exon
T4868 7901-7903 CD denotes 14
T4869 7904-7905 -LRB- denotes (
T4870 7912-7914 NN denotes 1A
T4871 7905-7911 NN denotes Figure
T4872 7914-7915 -RRB- denotes )
T4873 7915-7916 . denotes .
T4874 7916-8199 sentence denotes The transcript from loss of exon 14 results in a shift in the normal reading frame, resulting in a premature chain termination codon which, if utilized, would result in a truncated polypeptide that is 605 aa in length, of which the first 580 aa correspond to the normal Apc protein.
T4875 7917-7920 DT denotes The
T4876 7921-7931 NN denotes transcript
T4877 7953-7960 VBZ denotes results
T4878 7932-7936 IN denotes from
T4879 7937-7941 NN denotes loss
T4880 7942-7944 IN denotes of
T4881 7945-7949 NN denotes exon
T4882 7950-7952 CD denotes 14
T4883 7961-7963 IN denotes in
T4884 7964-7965 DT denotes a
T4885 7966-7971 NN denotes shift
T4886 7972-7974 IN denotes in
T4887 7975-7978 DT denotes the
T4888 7994-7999 NN denotes frame
T4889 7979-7985 JJ denotes normal
T4890 7986-7993 NN denotes reading
T4891 7999-8001 , denotes ,
T4892 8001-8010 VBG denotes resulting
T4893 8011-8013 IN denotes in
T4894 8014-8015 DT denotes a
T4895 8044-8049 NN denotes codon
T4896 8016-8025 JJ denotes premature
T4897 8026-8031 NN denotes chain
T4898 8032-8043 NN denotes termination
T4899 8050-8055 WDT denotes which
T4900 8076-8082 VB denotes result
T4901 8055-8057 , denotes ,
T4902 8057-8059 IN denotes if
T4903 8060-8068 VBN denotes utilized
T4904 8068-8070 , denotes ,
T4905 8070-8075 MD denotes would
T4906 8083-8085 IN denotes in
T4907 8086-8087 DT denotes a
T4908 8098-8109 NN denotes polypeptide
T4909 8088-8097 VBN denotes truncated
T4910 8110-8114 WDT denotes that
T4911 8115-8117 VBZ denotes is
T4912 8118-8121 CD denotes 605
T4913 8122-8124 NNS denotes aa
T4914 8125-8127 IN denotes in
T4915 8128-8134 NN denotes length
T4916 8134-8136 , denotes ,
T4917 8136-8138 IN denotes of
T4918 8162-8172 VBP denotes correspond
T4919 8139-8144 WDT denotes which
T4920 8145-8148 DT denotes the
T4921 8159-8161 NNS denotes aa
T4922 8149-8154 JJ denotes first
T4923 8155-8158 CD denotes 580
T4924 8173-8175 IN denotes to
T4925 8176-8179 DT denotes the
T4926 8191-8198 NN denotes protein
T4927 8180-8186 JJ denotes normal
T4928 8187-8190 NN denotes Apc
T4929 8198-8199 . denotes .
T4930 8199-9923 sentence denotes Figure 1 Generation of the Conditional Apc Allele (A) Schematic diagram of exons 14 and 15 of the mouse Apc gene, the targeting vector, and the resulting conditional allele with 2 LoxP sites sandwiching the exon 14. The PGK-neomycin cassette was inserted within intron 14 by recombineering technique. This cassette is sandwiched by 2 FRT sites that could be removed by crossing to FLPe-expressing mice. Positions of PCR primers used for genotyping PCR (F2, R2, R4) and RT-PCR (F546 and R721) are indicated. Positions of probe used for Southern blot analysis with NdeI sites are also shown. Upon Cre-mediated recombination, exon 14 is removed and leads to truncated Apc protein, of which the first 580 aa correspond to the normal. (B) Southern blot analysis of NdeI-digested genomic tail DNA isolated from F1 mice of various Apc mouse lines (ApcCKON, ApcΔ580), hybridized to a 600-bp probe. Tail genomic DNA from ApcCKON F1 mice derived from a modified ES clone showed a 12-kb band for the ApcCKON allele and a 10-kb band for the wild-type allele, whereas genomic DNA from the ApcΔ580 mouse was heterozygous for the ApcΔ580 allele (9.2-kb band). (C) Kaplan-Meier survival plot of ApcCKO/+ mice (thin solid line, n = 39), ApcCKO/CKO mice (thin dotted line, n = 57), ApcΔ580/+ mice (solid line, n = 51), and wild-type littermates (broken line, n = 21). Heterozygosity of the ApcΔ580 allele led to a significantly shortened survival (p < 0.0001), whereas those of heterozygous and homozygous ApcCKO mice had no significant difference to that of wild-type littermates. Southern blot analysis of tail DNA from F1 offspring of both ApcCKON and ApcΔ580 lines confirmed the germline transmission of modified Apc allele (Figure 1B).
T4931 9765-9773 NNP denotes Southern
T4932 9774-9778 NN denotes blot
T4933 9779-9787 NN denotes analysis
T4934 9852-9861 VBD denotes confirmed
T4935 9788-9790 IN denotes of
T4936 9791-9795 NN denotes tail
T4937 9796-9799 NN denotes DNA
T4938 9800-9804 IN denotes from
T4939 9805-9807 NN denotes F1
T4940 9808-9817 NN denotes offspring
T4941 9818-9820 IN denotes of
T4942 9821-9825 CC denotes both
T4943 9826-9833 NN denotes ApcCKON
T4944 9846-9851 NNS denotes lines
T4945 9834-9837 CC denotes and
T4946 9838-9845 NN denotes ApcΔ580
T4947 9862-9865 DT denotes the
T4948 9875-9887 NN denotes transmission
T4949 9866-9874 NN denotes germline
T4950 9888-9890 IN denotes of
T4951 9891-9899 VBN denotes modified
T4952 9904-9910 NN denotes allele
T4953 9900-9903 NN denotes Apc
T4954 9911-9912 -LRB- denotes (
T4955 9919-9921 NN denotes 1B
T4956 9912-9918 NN denotes Figure
T4957 9921-9922 -RRB- denotes )
T4958 9922-9923 . denotes .
T4959 9923-10037 sentence denotes Mice that are heterozygous for ApcΔ580 mutation are viable but have a significantly reduced lifespan (Figure 1C).
T4960 9924-9928 NNS denotes Mice
T4961 9972-9975 VBP denotes are
T4962 9929-9933 WDT denotes that
T4963 9934-9937 VBP denotes are
T4964 9938-9950 JJ denotes heterozygous
T4965 9951-9954 IN denotes for
T4966 9955-9962 NN denotes ApcΔ580
T4967 9963-9971 NN denotes mutation
T4968 9976-9982 JJ denotes viable
T4969 9983-9986 CC denotes but
T4970 9987-9991 VBP denotes have
T4971 9992-9993 DT denotes a
T4972 10016-10024 NN denotes lifespan
T4973 9994-10007 RB denotes significantly
T4974 10008-10015 VBN denotes reduced
T4975 10025-10026 -LRB- denotes (
T4976 10033-10035 NN denotes 1C
T4977 10026-10032 NN denotes Figure
T4978 10035-10036 -RRB- denotes )
T4979 10036-10037 . denotes .
T4980 10037-10162 sentence denotes These results suggested that deletion of exon 14 indeed results in either loss or abnormal function of the Apc gene product.
T4981 10038-10043 DT denotes These
T4982 10044-10051 NNS denotes results
T4983 10052-10061 VBD denotes suggested
T4984 10062-10066 IN denotes that
T4985 10094-10101 VBZ denotes results
T4986 10067-10075 NN denotes deletion
T4987 10076-10078 IN denotes of
T4988 10079-10083 NN denotes exon
T4989 10084-10086 CD denotes 14
T4990 10087-10093 RB denotes indeed
T4991 10102-10104 IN denotes in
T4992 10105-10111 CC denotes either
T4993 10112-10116 NN denotes loss
T4994 10117-10119 CC denotes or
T4995 10120-10128 JJ denotes abnormal
T4996 10129-10137 NN denotes function
T4997 10138-10140 IN denotes of
T4998 10141-10144 DT denotes the
T4999 10154-10161 NN denotes product
T5000 10145-10148 NN denotes Apc
T5001 10149-10153 NN denotes gene
T5002 10161-10162 . denotes .
T5003 10162-10280 sentence denotes ApcΔ580/+ mice have median survival of 5 mo of age (Figure 1C), with progressive signs of rectal bleeding and anemia.
T5004 10163-10170 NN denotes ApcΔ580
T5005 10173-10177 NNS denotes mice
T5006 10170-10171 HYPH denotes /
T5007 10171-10172 SYM denotes +
T5008 10178-10182 VBP denotes have
T5009 10183-10189 JJ denotes median
T5010 10190-10198 NN denotes survival
T5011 10199-10201 IN denotes of
T5012 10202-10203 CD denotes 5
T5013 10204-10206 NNS denotes mo
T5014 10207-10209 IN denotes of
T5015 10210-10213 NN denotes age
T5016 10214-10215 -LRB- denotes (
T5017 10222-10224 NN denotes 1C
T5018 10215-10221 NN denotes Figure
T5019 10224-10225 -RRB- denotes )
T5020 10225-10227 , denotes ,
T5021 10227-10231 IN denotes with
T5022 10232-10243 JJ denotes progressive
T5023 10244-10249 NNS denotes signs
T5024 10250-10252 IN denotes of
T5025 10253-10259 JJ denotes rectal
T5026 10260-10268 NN denotes bleeding
T5027 10269-10272 CC denotes and
T5028 10273-10279 NN denotes anemia
T5029 10279-10280 . denotes .
T5030 10280-10495 sentence denotes Similar to the results reported with an independently generated ApcΔ580/+ conditional mouse strain [14], ApcΔ580/+ mice had more than 100 (120 ± 37, n = 11) intestinal tumors at the time of their death (Figure S1).
T5031 10281-10288 JJ denotes Similar
T5032 10401-10404 VBD denotes had
T5033 10289-10291 IN denotes to
T5034 10292-10295 DT denotes the
T5035 10296-10303 NNS denotes results
T5036 10304-10312 VBN denotes reported
T5037 10313-10317 IN denotes with
T5038 10318-10320 DT denotes an
T5039 10373-10379 NN denotes strain
T5040 10321-10334 RB denotes independently
T5041 10335-10344 VBN denotes generated
T5042 10345-10352 NN denotes ApcΔ580
T5043 10355-10366 JJ denotes conditional
T5044 10352-10353 HYPH denotes /
T5045 10353-10354 SYM denotes +
T5046 10367-10372 NN denotes mouse
T5047 10380-10381 -LRB- denotes [
T5048 10381-10383 CD denotes 14
T5049 10383-10384 -RRB- denotes ]
T5050 10384-10386 , denotes ,
T5051 10386-10393 NN denotes ApcΔ580
T5052 10396-10400 NNS denotes mice
T5053 10393-10394 HYPH denotes /
T5054 10394-10395 SYM denotes +
T5055 10405-10409 JJR denotes more
T5056 10415-10418 CD denotes 100
T5057 10410-10414 IN denotes than
T5058 10449-10455 NNS denotes tumors
T5059 10419-10420 -LRB- denotes (
T5060 10426-10428 CD denotes 37
T5061 10420-10423 CD denotes 120
T5062 10424-10425 SYM denotes ±
T5063 10428-10430 , denotes ,
T5064 10430-10431 NN denotes n
T5065 10434-10436 CD denotes 11
T5066 10432-10433 SYM denotes =
T5067 10436-10437 -RRB- denotes )
T5068 10438-10448 JJ denotes intestinal
T5069 10456-10458 IN denotes at
T5070 10459-10462 DT denotes the
T5071 10463-10467 NN denotes time
T5072 10468-10470 IN denotes of
T5073 10471-10476 PRP$ denotes their
T5074 10477-10482 NN denotes death
T5075 10483-10484 -LRB- denotes (
T5076 10491-10493 NN denotes S1
T5077 10484-10490 NN denotes Figure
T5078 10493-10494 -RRB- denotes )
T5079 10494-10495 . denotes .
T5080 10495-10577 sentence denotes Inactivation of wild-type Apc is an important prerequisite for tumor development.
T5081 10496-10508 NN denotes Inactivation
T5082 10526-10528 VBZ denotes is
T5083 10509-10511 IN denotes of
T5084 10512-10516 JJ denotes wild
T5085 10517-10521 NN denotes type
T5086 10516-10517 HYPH denotes -
T5087 10522-10525 NN denotes Apc
T5088 10529-10531 DT denotes an
T5089 10542-10554 NN denotes prerequisite
T5090 10532-10541 JJ denotes important
T5091 10555-10558 IN denotes for
T5092 10559-10564 NN denotes tumor
T5093 10565-10576 NN denotes development
T5094 10576-10577 . denotes .
T5095 10577-10838 sentence denotes We analyzed 30 intestinal tumors from ApcΔ580/+ mice by in vitro transcription and translation assay, but none of them showed truncated Apc products (unpublished data), indicating that the most likely mechanism of wild-type Apc inactivation is by allelic loss.
T5096 10578-10580 PRP denotes We
T5097 10581-10589 VBD denotes analyzed
T5098 10590-10592 CD denotes 30
T5099 10604-10610 NNS denotes tumors
T5100 10593-10603 JJ denotes intestinal
T5101 10611-10615 IN denotes from
T5102 10616-10623 JJ denotes ApcΔ580
T5103 10626-10630 NNS denotes mice
T5104 10623-10624 HYPH denotes /
T5105 10624-10625 SYM denotes +
T5106 10631-10633 IN denotes by
T5107 10634-10636 FW denotes in
T5108 10637-10642 FW denotes vitro
T5109 10643-10656 NN denotes transcription
T5110 10657-10660 CC denotes and
T5111 10661-10672 NN denotes translation
T5112 10673-10678 NN denotes assay
T5113 10678-10680 , denotes ,
T5114 10680-10683 CC denotes but
T5115 10684-10688 NN denotes none
T5116 10697-10703 VBD denotes showed
T5117 10689-10691 IN denotes of
T5118 10692-10696 PRP denotes them
T5119 10704-10713 VBN denotes truncated
T5120 10718-10726 NNS denotes products
T5121 10714-10717 NN denotes Apc
T5122 10727-10728 -LRB- denotes (
T5123 10740-10744 NNS denotes data
T5124 10728-10739 JJ denotes unpublished
T5125 10744-10745 -RRB- denotes )
T5126 10745-10747 , denotes ,
T5127 10747-10757 VBG denotes indicating
T5128 10758-10762 IN denotes that
T5129 10819-10821 VBZ denotes is
T5130 10763-10766 DT denotes the
T5131 10779-10788 NN denotes mechanism
T5132 10767-10771 RBS denotes most
T5133 10772-10778 JJ denotes likely
T5134 10789-10791 IN denotes of
T5135 10792-10796 JJ denotes wild
T5136 10797-10801 NN denotes type
T5137 10796-10797 HYPH denotes -
T5138 10806-10818 NN denotes inactivation
T5139 10802-10805 NN denotes Apc
T5140 10822-10824 IN denotes by
T5141 10825-10832 JJ denotes allelic
T5142 10833-10837 NN denotes loss
T5143 10837-10838 . denotes .
T5144 10838-11036 sentence denotes The mutant allele had to be maintained and transmitted through male mice, as ApcΔ580/+ females were frequently not healthy enough to successfully nurse their own pups because of their tumor burden.
T5145 10839-10842 DT denotes The
T5146 10850-10856 NN denotes allele
T5147 10843-10849 JJ denotes mutant
T5148 10857-10860 VBD denotes had
T5149 10861-10863 TO denotes to
T5150 10867-10877 VBN denotes maintained
T5151 10864-10866 VB denotes be
T5152 10878-10881 CC denotes and
T5153 10882-10893 VBN denotes transmitted
T5154 10894-10901 IN denotes through
T5155 10902-10906 JJ denotes male
T5156 10907-10911 NNS denotes mice
T5157 10911-10913 , denotes ,
T5158 10913-10915 IN denotes as
T5159 10934-10938 VBD denotes were
T5160 10916-10923 NN denotes ApcΔ580
T5161 10926-10933 NNS denotes females
T5162 10923-10924 HYPH denotes /
T5163 10924-10925 SYM denotes +
T5164 10939-10949 RB denotes frequently
T5165 10950-10953 RB denotes not
T5166 10954-10961 JJ denotes healthy
T5167 10962-10968 RB denotes enough
T5168 10969-10971 TO denotes to
T5169 10985-10990 VB denotes nurse
T5170 10972-10984 RB denotes successfully
T5171 10991-10996 PRP$ denotes their
T5172 11001-11005 NNS denotes pups
T5173 10997-11000 JJ denotes own
T5174 11006-11013 IN denotes because
T5175 11014-11016 IN denotes of
T5176 11017-11022 PRP$ denotes their
T5177 11029-11035 NN denotes burden
T5178 11023-11028 NN denotes tumor
T5179 11035-11036 . denotes .
T5180 11036-11102 sentence denotes ApcCKO/+ mice were intercrossed to generate ApcCKO/CKO offspring.
T5181 11037-11043 NN denotes ApcCKO
T5182 11046-11050 NNS denotes mice
T5183 11043-11044 HYPH denotes /
T5184 11044-11045 SYM denotes +
T5185 11056-11068 VBN denotes intercrossed
T5186 11051-11055 VBD denotes were
T5187 11069-11071 TO denotes to
T5188 11072-11080 VB denotes generate
T5189 11081-11087 NN denotes ApcCKO
T5190 11088-11091 NN denotes CKO
T5191 11087-11088 HYPH denotes /
T5192 11092-11101 NN denotes offspring
T5193 11101-11102 . denotes .
T5194 11102-11195 sentence denotes Approximately one-quarter of the offspring (17 of 81) were homozygous for the ApcCKO allele.
T5195 11103-11116 RB denotes Approximately
T5196 11117-11120 CD denotes one
T5197 11157-11161 VBD denotes were
T5198 11120-11121 HYPH denotes -
T5199 11121-11128 JJ denotes quarter
T5200 11129-11131 IN denotes of
T5201 11132-11135 DT denotes the
T5202 11136-11145 NN denotes offspring
T5203 11146-11147 -LRB- denotes (
T5204 11147-11149 CD denotes 17
T5205 11150-11152 IN denotes of
T5206 11153-11155 CD denotes 81
T5207 11155-11156 -RRB- denotes )
T5208 11162-11172 JJ denotes homozygous
T5209 11173-11176 IN denotes for
T5210 11177-11180 DT denotes the
T5211 11188-11194 NN denotes allele
T5212 11181-11187 NN denotes ApcCKO
T5213 11194-11195 . denotes .
T5214 11195-11348 sentence denotes These mice as well as heterozygous mice for ApcCKO allele are normal, showing no differences in their survival to the wild-type littermates (Figure 1C).
T5215 11196-11201 DT denotes These
T5216 11202-11206 NNS denotes mice
T5217 11254-11257 VBP denotes are
T5218 11207-11209 RB denotes as
T5219 11215-11217 IN denotes as
T5220 11210-11214 RB denotes well
T5221 11218-11230 JJ denotes heterozygous
T5222 11231-11235 NNS denotes mice
T5223 11236-11239 IN denotes for
T5224 11240-11246 NN denotes ApcCKO
T5225 11247-11253 NN denotes allele
T5226 11258-11264 JJ denotes normal
T5227 11264-11266 , denotes ,
T5228 11266-11273 VBG denotes showing
T5229 11274-11276 DT denotes no
T5230 11277-11288 NNS denotes differences
T5231 11289-11291 IN denotes in
T5232 11292-11297 PRP$ denotes their
T5233 11298-11306 NN denotes survival
T5234 11307-11309 IN denotes to
T5235 11310-11313 DT denotes the
T5236 11324-11335 NNS denotes littermates
T5237 11314-11318 JJ denotes wild
T5238 11319-11323 NN denotes type
T5239 11318-11319 HYPH denotes -
T5240 11336-11337 -LRB- denotes (
T5241 11344-11346 NN denotes 1C
T5242 11337-11343 NN denotes Figure
T5243 11346-11347 -RRB- denotes )
T5244 11347-11348 . denotes .
T5245 11348-11481 sentence denotes We tested whether our ApcCKO allele can compliment the wild-type allele by crossing the ApcCKO/CKO female with ApcΔ580/+ male mouse.
T5246 11349-11351 PRP denotes We
T5247 11352-11358 VBD denotes tested
T5248 11359-11366 IN denotes whether
T5249 11389-11399 VB denotes compliment
T5250 11367-11370 PRP$ denotes our
T5251 11378-11384 NN denotes allele
T5252 11371-11377 NN denotes ApcCKO
T5253 11385-11388 MD denotes can
T5254 11400-11403 DT denotes the
T5255 11414-11420 NN denotes allele
T5256 11404-11408 JJ denotes wild
T5257 11409-11413 NN denotes type
T5258 11408-11409 HYPH denotes -
T5259 11421-11423 IN denotes by
T5260 11424-11432 VBG denotes crossing
T5261 11433-11436 DT denotes the
T5262 11448-11454 NN denotes female
T5263 11437-11443 NN denotes ApcCKO
T5264 11444-11447 NN denotes CKO
T5265 11443-11444 HYPH denotes /
T5266 11455-11459 IN denotes with
T5267 11460-11467 NN denotes ApcΔ580
T5268 11475-11480 NN denotes mouse
T5269 11467-11468 HYPH denotes /
T5270 11468-11469 SYM denotes +
T5271 11470-11474 JJ denotes male
T5272 11480-11481 . denotes .
T5273 11481-11689 sentence denotes The resultant ApcCKO/Δ580 offspring were viable and born in the Mendelian ratio, suggesting that the presence of loxP sites in introns flanking exon 14 have no adverse effect on the function of the Apc gene.
T5274 11482-11485 DT denotes The
T5275 11508-11517 NN denotes offspring
T5276 11486-11495 JJ denotes resultant
T5277 11496-11502 NN denotes ApcCKO
T5278 11503-11507 NN denotes Δ580
T5279 11502-11503 HYPH denotes /
T5280 11518-11522 VBD denotes were
T5281 11523-11529 JJ denotes viable
T5282 11530-11533 CC denotes and
T5283 11534-11538 VBN denotes born
T5284 11539-11541 IN denotes in
T5285 11542-11545 DT denotes the
T5286 11556-11561 NN denotes ratio
T5287 11546-11555 JJ denotes Mendelian
T5288 11561-11563 , denotes ,
T5289 11563-11573 VBG denotes suggesting
T5290 11574-11578 IN denotes that
T5291 11634-11638 VBP denotes have
T5292 11579-11582 DT denotes the
T5293 11583-11591 NN denotes presence
T5294 11592-11594 IN denotes of
T5295 11595-11599 NN denotes loxP
T5296 11600-11605 NNS denotes sites
T5297 11606-11608 IN denotes in
T5298 11609-11616 NNS denotes introns
T5299 11617-11625 VBG denotes flanking
T5300 11626-11630 NN denotes exon
T5301 11631-11633 CD denotes 14
T5302 11639-11641 DT denotes no
T5303 11650-11656 NN denotes effect
T5304 11642-11649 JJ denotes adverse
T5305 11657-11659 IN denotes on
T5306 11660-11663 DT denotes the
T5307 11664-11672 NN denotes function
T5308 11673-11675 IN denotes of
T5309 11676-11679 DT denotes the
T5310 11684-11688 NN denotes gene
T5311 11680-11683 NN denotes Apc
T5312 11688-11689 . denotes .
T7674 11691-11694 NN denotes K14
T7675 11695-11701 VBN denotes Driven
T7676 11694-11695 HYPH denotes -
T7677 11702-11706 NN denotes Loss
T7678 11714-11721 VBZ denotes Results
T7679 11707-11709 IN denotes of
T7680 11710-11713 NN denotes Apc
T7681 11722-11724 IN denotes in
T7682 11725-11731 JJ denotes Severe
T7683 11739-11750 NN denotes Retardation
T7684 11732-11738 NN denotes Growth
T7685 11751-11754 CC denotes and
T7686 11755-11760 JJ denotes Early
T7687 11761-11770 NN denotes Lethality
T7688 11770-11934 sentence denotes To introduce the mutation of Apc into cells expressing K14, we crossed WW6 ES cell–derived [15] ApcCKO/+ mice with K14-cre recombinase mice in FVB background [16].
T7689 11771-11773 TO denotes To
T7690 11774-11783 VB denotes introduce
T7691 11834-11841 VBD denotes crossed
T7692 11784-11787 DT denotes the
T7693 11788-11796 NN denotes mutation
T7694 11797-11799 IN denotes of
T7695 11800-11803 NN denotes Apc
T7696 11804-11808 IN denotes into
T7697 11809-11814 NNS denotes cells
T7698 11815-11825 VBG denotes expressing
T7699 11826-11829 NN denotes K14
T7700 11829-11831 , denotes ,
T7701 11831-11833 PRP denotes we
T7702 11842-11845 NN denotes WW6
T7703 11876-11880 NNS denotes mice
T7704 11846-11848 NN denotes ES
T7705 11849-11853 NN denotes cell
T7706 11854-11861 VBN denotes derived
T7707 11853-11854 HYPH denotes
T7708 11862-11863 -LRB- denotes [
T7709 11863-11865 CD denotes 15
T7710 11865-11866 -RRB- denotes ]
T7711 11867-11873 NN denotes ApcCKO
T7712 11873-11874 HYPH denotes /
T7713 11874-11875 SYM denotes +
T7714 11881-11885 IN denotes with
T7715 11886-11889 NN denotes K14
T7716 11890-11893 NN denotes cre
T7717 11889-11890 HYPH denotes -
T7718 11906-11910 NNS denotes mice
T7719 11894-11905 NN denotes recombinase
T7720 11911-11913 IN denotes in
T7721 11914-11917 NN denotes FVB
T7722 11918-11928 NN denotes background
T7723 11929-11930 -LRB- denotes [
T7724 11930-11932 CD denotes 16
T7725 11932-11933 -RRB- denotes ]
T7726 11933-11934 . denotes .
T7727 11934-12005 sentence denotes The K14-cre; ApcCKO/+ mice were normal in appearance and were fertile.
T7728 11935-11938 DT denotes The
T7729 11957-11961 NNS denotes mice
T7730 11939-11942 NN denotes K14
T7731 11943-11946 NN denotes cre
T7732 11942-11943 HYPH denotes -
T7733 11946-11947 : denotes ;
T7734 11948-11954 NN denotes ApcCKO
T7735 11954-11955 HYPH denotes /
T7736 11955-11956 SYM denotes +
T7737 11962-11966 VBD denotes were
T7738 11967-11973 JJ denotes normal
T7739 11974-11976 IN denotes in
T7740 11977-11987 NN denotes appearance
T7741 11988-11991 CC denotes and
T7742 11992-11996 VBD denotes were
T7743 11997-12004 JJ denotes fertile
T7744 12004-12005 . denotes .
T7745 12005-12147 sentence denotes K14-cre; ApcCKO/+ males were crossed to ApcCKO/CKO females to avoid the potential deleter effect in oocytes of K14-cre–positive females [17].
T7746 12006-12009 NN denotes K14
T7747 12010-12013 NN denotes cre
T7748 12009-12010 HYPH denotes -
T7749 12024-12029 NNS denotes males
T7750 12013-12014 : denotes ;
T7751 12015-12021 NN denotes ApcCKO
T7752 12021-12022 HYPH denotes /
T7753 12022-12023 SYM denotes +
T7754 12035-12042 VBN denotes crossed
T7755 12030-12034 VBD denotes were
T7756 12043-12045 IN denotes to
T7757 12046-12052 NN denotes ApcCKO
T7758 12053-12056 NN denotes CKO
T7759 12052-12053 HYPH denotes /
T7760 12057-12064 NNS denotes females
T7761 12065-12067 TO denotes to
T7762 12068-12073 VB denotes avoid
T7763 12074-12077 DT denotes the
T7764 12096-12102 NN denotes effect
T7765 12078-12087 JJ denotes potential
T7766 12088-12095 NN denotes deleter
T7767 12103-12105 IN denotes in
T7768 12106-12113 NNS denotes oocytes
T7769 12114-12116 IN denotes of
T7770 12117-12120 NN denotes K14
T7771 12121-12124 NN denotes cre
T7772 12120-12121 HYPH denotes -
T7773 12125-12133 JJ denotes positive
T7774 12124-12125 HYPH denotes
T7775 12134-12141 NNS denotes females
T7776 12142-12143 -LRB- denotes [
T7777 12143-12145 CD denotes 17
T7778 12145-12146 -RRB- denotes ]
T7779 12146-12147 . denotes .
T7780 12147-12347 sentence denotes The mice were intercrossed thereafter for maintenance; hence, the mice used for analysis were in a mixed background of FVB, 129/S, and C57BL/6 in similar proportions, with minimal contribution of SJ.
T7781 12148-12151 DT denotes The
T7782 12152-12156 NNS denotes mice
T7783 12162-12174 VBN denotes intercrossed
T7784 12157-12161 VBD denotes were
T7785 12237-12241 VBD denotes were
T7786 12175-12185 RB denotes thereafter
T7787 12186-12189 IN denotes for
T7788 12190-12201 NN denotes maintenance
T7789 12201-12202 : denotes ;
T7790 12203-12208 RB denotes hence
T7791 12208-12210 , denotes ,
T7792 12210-12213 DT denotes the
T7793 12214-12218 NNS denotes mice
T7794 12219-12223 VBN denotes used
T7795 12224-12227 IN denotes for
T7796 12228-12236 NN denotes analysis
T7797 12242-12244 IN denotes in
T7798 12245-12246 DT denotes a
T7799 12253-12263 NN denotes background
T7800 12247-12252 VBN denotes mixed
T7801 12264-12266 IN denotes of
T7802 12267-12270 NN denotes FVB
T7803 12270-12272 , denotes ,
T7804 12272-12275 CD denotes 129
T7805 12276-12277 NN denotes S
T7806 12275-12276 HYPH denotes /
T7807 12277-12279 , denotes ,
T7808 12279-12282 CC denotes and
T7809 12283-12288 NN denotes C57BL
T7810 12288-12289 HYPH denotes /
T7811 12289-12290 CD denotes 6
T7812 12291-12293 IN denotes in
T7813 12294-12301 JJ denotes similar
T7814 12302-12313 NNS denotes proportions
T7815 12313-12315 , denotes ,
T7816 12315-12319 IN denotes with
T7817 12320-12327 JJ denotes minimal
T7818 12328-12340 NN denotes contribution
T7819 12341-12343 IN denotes of
T7820 12344-12346 NN denotes SJ
T7821 12346-12347 . denotes .
T7822 12347-12653 sentence denotes The K14 promoter is a commonly used epidermal cell promoter because of its expression by the mitotically active cells of the epidermis and its appendages in mature skin [18], but most notably it is active in embryonic ectoderm as early as the single layered ectodermal stage of embryonic day (E) 9.5 [19].
T7823 12348-12351 DT denotes The
T7824 12356-12364 NN denotes promoter
T7825 12352-12355 NN denotes K14
T7826 12365-12367 VBZ denotes is
T7827 12368-12369 DT denotes a
T7828 12399-12407 NN denotes promoter
T7829 12370-12378 RB denotes commonly
T7830 12379-12383 VBN denotes used
T7831 12384-12393 JJ denotes epidermal
T7832 12394-12398 NN denotes cell
T7833 12408-12415 IN denotes because
T7834 12416-12418 IN denotes of
T7835 12419-12422 PRP$ denotes its
T7836 12423-12433 NN denotes expression
T7837 12434-12436 IN denotes by
T7838 12437-12440 DT denotes the
T7839 12460-12465 NNS denotes cells
T7840 12441-12452 RB denotes mitotically
T7841 12453-12459 JJ denotes active
T7842 12466-12468 IN denotes of
T7843 12469-12472 DT denotes the
T7844 12473-12482 NN denotes epidermis
T7845 12483-12486 CC denotes and
T7846 12487-12490 PRP$ denotes its
T7847 12491-12501 NNS denotes appendages
T7848 12502-12504 IN denotes in
T7849 12505-12511 JJ denotes mature
T7850 12512-12516 NN denotes skin
T7851 12517-12518 -LRB- denotes [
T7852 12518-12520 CD denotes 18
T7853 12520-12521 -RRB- denotes ]
T7854 12521-12523 , denotes ,
T7855 12523-12526 CC denotes but
T7856 12527-12531 RBS denotes most
T7857 12532-12539 RB denotes notably
T7858 12543-12545 VBZ denotes is
T7859 12540-12542 PRP denotes it
T7860 12546-12552 JJ denotes active
T7861 12553-12555 IN denotes in
T7862 12556-12565 JJ denotes embryonic
T7863 12566-12574 NN denotes ectoderm
T7864 12575-12577 RB denotes as
T7865 12578-12583 RB denotes early
T7866 12584-12586 IN denotes as
T7867 12587-12590 DT denotes the
T7868 12617-12622 NN denotes stage
T7869 12591-12597 JJ denotes single
T7870 12598-12605 VBN denotes layered
T7871 12606-12616 JJ denotes ectodermal
T7872 12623-12625 IN denotes of
T7873 12626-12635 JJ denotes embryonic
T7874 12636-12639 NN denotes day
T7875 12640-12641 -LRB- denotes (
T7876 12641-12642 NN denotes E
T7877 12642-12643 -RRB- denotes )
T7878 12644-12647 CD denotes 9.5
T7879 12648-12649 -LRB- denotes [
T7880 12649-12651 CD denotes 19
T7881 12651-12652 -RRB- denotes ]
T7882 12652-12653 . denotes .
T7883 12653-12770 sentence denotes A restricted expression of K14 is also found in thymic epithelial cells (TECs) in the medulla of normal thymus [20].
T7884 12654-12655 DT denotes A
T7885 12667-12677 NN denotes expression
T7886 12656-12666 JJ denotes restricted
T7887 12693-12698 VBN denotes found
T7888 12678-12680 IN denotes of
T7889 12681-12684 NN denotes K14
T7890 12685-12687 VBZ denotes is
T7891 12688-12692 RB denotes also
T7892 12699-12701 IN denotes in
T7893 12702-12708 JJ denotes thymic
T7894 12720-12725 NNS denotes cells
T7895 12709-12719 JJ denotes epithelial
T7896 12726-12727 -LRB- denotes (
T7897 12727-12731 NNS denotes TECs
T7898 12731-12732 -RRB- denotes )
T7899 12733-12735 IN denotes in
T7900 12736-12739 DT denotes the
T7901 12740-12747 NN denotes medulla
T7902 12748-12750 IN denotes of
T7903 12751-12757 JJ denotes normal
T7904 12758-12764 NN denotes thymus
T7905 12765-12766 -LRB- denotes [
T7906 12766-12768 CD denotes 20
T7907 12768-12769 -RRB- denotes ]
T7908 12769-12770 . denotes .
T7909 12770-12902 sentence denotes We genotyped a total of 458 pups (8–10 d old) from 67 litters resulting from crosses between K14-cre; ApcCKO/+ and ApcCKO/CKO mice.
T7910 12771-12773 PRP denotes We
T7911 12774-12783 VBD denotes genotyped
T7912 12784-12785 DT denotes a
T7913 12795-12798 CD denotes 458
T7914 12786-12791 NN denotes total
T7915 12792-12794 IN denotes of
T7916 12799-12803 NNS denotes pups
T7917 12804-12805 -LRB- denotes (
T7918 12812-12815 JJ denotes old
T7919 12805-12806 CD denotes 8
T7920 12807-12809 CD denotes 10
T7921 12806-12807 SYM denotes
T7922 12810-12811 NNS denotes d
T7923 12815-12816 -RRB- denotes )
T7924 12817-12821 IN denotes from
T7925 12822-12824 CD denotes 67
T7926 12825-12832 NNS denotes litters
T7927 12833-12842 VBG denotes resulting
T7928 12843-12847 IN denotes from
T7929 12848-12855 NNS denotes crosses
T7930 12856-12863 IN denotes between
T7931 12864-12867 NN denotes K14
T7932 12868-12871 NN denotes cre
T7933 12867-12868 HYPH denotes -
T7934 12897-12901 NNS denotes mice
T7935 12871-12872 : denotes ;
T7936 12873-12879 NN denotes ApcCKO
T7937 12879-12880 HYPH denotes /
T7938 12880-12881 SYM denotes +
T7939 12882-12885 CC denotes and
T7940 12886-12892 NN denotes ApcCKO
T7941 12893-12896 NN denotes CKO
T7942 12892-12893 HYPH denotes /
T7943 12901-12902 . denotes .
T7944 12902-13119 sentence denotes The mutant mice of the genotype K14-cre; ApcCKO/CKO (hereafter, KA mutant) were born, but the observed frequency of KA mutants was much less than expected (78 of 458 [17.0%]; p < 0.0005 Chi-square analysis, Table 1).
T7945 12903-12906 DT denotes The
T7946 12914-12918 NNS denotes mice
T7947 12907-12913 JJ denotes mutant
T7948 12983-12987 VBN denotes born
T7949 12919-12921 IN denotes of
T7950 12922-12925 DT denotes the
T7951 12926-12934 NN denotes genotype
T7952 12935-12938 NN denotes K14
T7953 12939-12942 NN denotes cre
T7954 12938-12939 HYPH denotes -
T7955 12942-12943 : denotes ;
T7956 12944-12950 NN denotes ApcCKO
T7957 12951-12954 NN denotes CKO
T7958 12950-12951 HYPH denotes /
T7959 12955-12956 -LRB- denotes (
T7960 12970-12976 NN denotes mutant
T7961 12956-12965 RB denotes hereafter
T7962 12965-12967 , denotes ,
T7963 12967-12969 NN denotes KA
T7964 12976-12977 -RRB- denotes )
T7965 12978-12982 VBD denotes were
T7966 12987-12989 , denotes ,
T7967 12989-12992 CC denotes but
T7968 12993-12996 DT denotes the
T7969 13006-13015 NN denotes frequency
T7970 12997-13005 VBN denotes observed
T7971 13030-13033 VBD denotes was
T7972 13016-13018 IN denotes of
T7973 13019-13021 NN denotes KA
T7974 13022-13029 NNS denotes mutants
T7975 13034-13038 RB denotes much
T7976 13039-13043 JJR denotes less
T7977 13044-13048 IN denotes than
T7978 13049-13057 VBN denotes expected
T7979 13058-13059 -LRB- denotes (
T7980 13110-13115 NN denotes Table
T7981 13059-13061 CD denotes 78
T7982 13062-13064 IN denotes of
T7983 13065-13068 CD denotes 458
T7984 13069-13070 -LRB- denotes [
T7985 13074-13075 NN denotes %
T7986 13070-13074 CD denotes 17.0
T7987 13075-13076 -RRB- denotes ]
T7988 13076-13077 : denotes ;
T7989 13078-13079 NN denotes p
T7990 13100-13108 NN denotes analysis
T7991 13080-13081 SYM denotes <
T7992 13082-13088 CD denotes 0.0005
T7993 13089-13092 NN denotes Chi
T7994 13093-13099 NN denotes square
T7995 13092-13093 HYPH denotes -
T7996 13108-13110 , denotes ,
T7997 13116-13117 CD denotes 1
T7998 13117-13118 -RRB- denotes )
T7999 13118-13119 . denotes .
T8000 13119-13282 sentence denotes To assess the basis for the neonatal lethality of KA mutants, we monitored three litters from birth to weaning by measuring the body weight of each pup every day.
T8001 13120-13122 TO denotes To
T8002 13123-13129 VB denotes assess
T8003 13185-13194 VBD denotes monitored
T8004 13130-13133 DT denotes the
T8005 13134-13139 NN denotes basis
T8006 13140-13143 IN denotes for
T8007 13144-13147 DT denotes the
T8008 13157-13166 NN denotes lethality
T8009 13148-13156 JJ denotes neonatal
T8010 13167-13169 IN denotes of
T8011 13170-13172 NN denotes KA
T8012 13173-13180 NNS denotes mutants
T8013 13180-13182 , denotes ,
T8014 13182-13184 PRP denotes we
T8015 13195-13200 CD denotes three
T8016 13201-13208 NNS denotes litters
T8017 13209-13213 IN denotes from
T8018 13214-13219 NN denotes birth
T8019 13220-13222 IN denotes to
T8020 13223-13230 VBG denotes weaning
T8021 13231-13233 IN denotes by
T8022 13234-13243 VBG denotes measuring
T8023 13244-13247 DT denotes the
T8024 13253-13259 NN denotes weight
T8025 13248-13252 NN denotes body
T8026 13260-13262 IN denotes of
T8027 13263-13267 DT denotes each
T8028 13268-13271 NN denotes pup
T8029 13272-13277 DT denotes every
T8030 13278-13281 NN denotes day
T8031 13281-13282 . denotes .
T8032 13282-13474 sentence denotes A total of 25 pups were born from three litters, of which 7 (28%) were confirmed to be K14-cre; ApcCKO/CKO by genotyping, indicating that KA mutants were born in the expected Mendelian ratio.
T8033 13283-13284 DT denotes A
T8034 13294-13296 CD denotes 25
T8035 13285-13290 NN denotes total
T8036 13291-13293 IN denotes of
T8037 13297-13301 NNS denotes pups
T8038 13307-13311 VBN denotes born
T8039 13302-13306 VBD denotes were
T8040 13312-13316 IN denotes from
T8041 13317-13322 CD denotes three
T8042 13323-13330 NNS denotes litters
T8043 13330-13332 , denotes ,
T8044 13332-13334 IN denotes of
T8045 13354-13363 VBN denotes confirmed
T8046 13335-13340 WDT denotes which
T8047 13341-13342 CD denotes 7
T8048 13343-13344 -LRB- denotes (
T8049 13346-13347 NN denotes %
T8050 13344-13346 CD denotes 28
T8051 13347-13348 -RRB- denotes )
T8052 13349-13353 VBD denotes were
T8053 13364-13366 TO denotes to
T8054 13367-13369 VB denotes be
T8055 13370-13373 NN denotes K14
T8056 13374-13377 NN denotes cre
T8057 13373-13374 HYPH denotes -
T8058 13377-13378 : denotes ;
T8059 13379-13385 NN denotes ApcCKO
T8060 13386-13389 NN denotes CKO
T8061 13385-13386 HYPH denotes /
T8062 13390-13392 IN denotes by
T8063 13393-13403 NN denotes genotyping
T8064 13403-13405 , denotes ,
T8065 13405-13415 VBG denotes indicating
T8066 13416-13420 IN denotes that
T8067 13437-13441 VBN denotes born
T8068 13421-13423 NN denotes KA
T8069 13424-13431 NNS denotes mutants
T8070 13432-13436 VBD denotes were
T8071 13442-13444 IN denotes in
T8072 13445-13448 DT denotes the
T8073 13468-13473 NN denotes ratio
T8074 13449-13457 VBN denotes expected
T8075 13458-13467 JJ denotes Mendelian
T8076 13473-13474 . denotes .
T8077 13474-13629 sentence denotes The KA mutant pups were nursed normally, and there was milk in their stomachs during the first 2 or 3 d after birth, but they failed to thrive (Figure 2).
T8078 13475-13478 DT denotes The
T8079 13489-13493 NNS denotes pups
T8080 13479-13481 NN denotes KA
T8081 13482-13488 JJ denotes mutant
T8082 13499-13505 VBN denotes nursed
T8083 13494-13498 VBD denotes were
T8084 13506-13514 RB denotes normally
T8085 13514-13516 , denotes ,
T8086 13516-13519 CC denotes and
T8087 13520-13525 EX denotes there
T8088 13526-13529 VBD denotes was
T8089 13530-13534 NN denotes milk
T8090 13535-13537 IN denotes in
T8091 13538-13543 PRP$ denotes their
T8092 13544-13552 NNS denotes stomachs
T8093 13553-13559 IN denotes during
T8094 13560-13563 DT denotes the
T8095 13577-13578 NNS denotes d
T8096 13564-13569 JJ denotes first
T8097 13570-13571 CD denotes 2
T8098 13572-13574 CC denotes or
T8099 13575-13576 CD denotes 3
T8100 13579-13584 IN denotes after
T8101 13585-13590 NN denotes birth
T8102 13590-13592 , denotes ,
T8103 13592-13595 CC denotes but
T8104 13596-13600 PRP denotes they
T8105 13601-13607 VBD denotes failed
T8106 13608-13610 TO denotes to
T8107 13611-13617 VB denotes thrive
T8108 13618-13619 -LRB- denotes (
T8109 13619-13625 NN denotes Figure
T8110 13626-13627 CD denotes 2
T8111 13627-13628 -RRB- denotes )
T8112 13628-13629 . denotes .
T8113 13629-13811 sentence denotes By postnatal day (P) 8–10, at the time of genotyping, many KA mutant pups were considerably smaller than their littermates (Figure 2B–2F) and some have died at or prior to this age.
T8114 13630-13632 IN denotes By
T8115 13704-13708 VBD denotes were
T8116 13633-13642 JJ denotes postnatal
T8117 13643-13646 NN denotes day
T8118 13647-13648 -LRB- denotes (
T8119 13648-13649 NN denotes P
T8120 13649-13650 -RRB- denotes )
T8121 13651-13652 CD denotes 8
T8122 13652-13653 SYM denotes
T8123 13653-13655 CD denotes 10
T8124 13655-13657 , denotes ,
T8125 13657-13659 IN denotes at
T8126 13660-13663 DT denotes the
T8127 13664-13668 NN denotes time
T8128 13669-13671 IN denotes of
T8129 13672-13682 NN denotes genotyping
T8130 13682-13684 , denotes ,
T8131 13684-13688 JJ denotes many
T8132 13699-13703 NNS denotes pups
T8133 13689-13691 NN denotes KA
T8134 13692-13698 JJ denotes mutant
T8135 13709-13721 RB denotes considerably
T8136 13722-13729 JJR denotes smaller
T8137 13730-13734 IN denotes than
T8138 13735-13740 PRP$ denotes their
T8139 13741-13752 NNS denotes littermates
T8140 13753-13754 -LRB- denotes (
T8141 13761-13763 NN denotes 2B
T8142 13754-13760 NN denotes Figure
T8143 13763-13764 SYM denotes
T8144 13764-13766 NN denotes 2F
T8145 13766-13767 -RRB- denotes )
T8146 13768-13771 CC denotes and
T8147 13772-13776 DT denotes some
T8148 13782-13786 VBN denotes died
T8149 13777-13781 VBP denotes have
T8150 13787-13789 IN denotes at
T8151 13790-13792 CC denotes or
T8152 13793-13798 JJ denotes prior
T8153 13799-13801 IN denotes to
T8154 13802-13806 DT denotes this
T8155 13807-13810 NN denotes age
T8156 13810-13811 . denotes .
T8157 13811-13855 sentence denotes None of KA mutants survived to weaning age.
T8158 13812-13816 NN denotes None
T8159 13831-13839 VBD denotes survived
T8160 13817-13819 IN denotes of
T8161 13820-13822 NN denotes KA
T8162 13823-13830 NNS denotes mutants
T8163 13840-13842 IN denotes to
T8164 13843-13850 VBG denotes weaning
T8165 13851-13854 NN denotes age
T8166 13854-13855 . denotes .
T8167 13855-15400 sentence denotes Table 1 Genotype Distribution of Progeny from the Matings Figure 2 Postnatal Mortality and Stunted Growth in K14-cre; ApcCKO/CKO Mutant Mice Animals whose genotype is either heterozygous or homozygous for the wild-type Apc allele are referred to as normal (N); those whose genotype are K14-cre; ApcCKO/CKO and show the presence of K14-cre–recombined mutant Apc allele are called mutant (M). (A) Two P3 mutant mice, M1 and M2, and their normal littermates, showing size variation among mutants. (B) P8 mutant mouse (right) and a normal littermate. Note sparseness of hair coat and abnormal ears. (C–D) Vibrissae of whisker pads are short and oddly angled in a P12 mutant mouse (C), relative to control (D). Note the lack of incisors in the mutant. (E) A P17 mutant mouse (right) with its littermate. Its bare forehead, dorsal median line, and abnormal ears are evident. (F) Growth curve of mutants and normal littermates. Mutants exhibit stunted growth, which became more prominent as they aged, and weigh significantly less than littermates from P8 (p < 0.05). (G) Comparison of mutant and normal thymus from P3 mice. The mutant thymus (left) is dramatically smaller for its age compared to the normal littermate (right). The scale bar equals 1 mm. (H) Skeletal preparations of normal (left) and mutant (right), showing differences in development of both incisor (I) and molar (M) teeth. The ability of whole embryos to exclude blue dye was used to examine the epidermal barrier, normally acquired beginning at E16 and complete by E18.5 [21].
T8168 13856-15249 DT denotes Table 1 Genotype Distribution of Progeny from the Matings Figure 2 Postnatal Mortality and Stunted Growth in K14-cre; ApcCKO/CKO Mutant Mice Animals whose genotype is either heterozygous or homozygous for the wild-type Apc allele are referred to as normal (N); those whose genotype are K14-cre; ApcCKO/CKO and show the presence of K14-cre–recombined mutant Apc allele are called mutant (M). (A) Two P3 mutant mice, M1 and M2, and their normal littermates, showing size variation among mutants. (B) P8 mutant mouse (right) and a normal littermate. Note sparseness of hair coat and abnormal ears. (C–D) Vibrissae of whisker pads are short and oddly angled in a P12 mutant mouse (C), relative to control (D). Note the lack of incisors in the mutant. (E) A P17 mutant mouse (right) with its littermate. Its bare forehead, dorsal median line, and abnormal ears are evident. (F) Growth curve of mutants and normal littermates. Mutants exhibit stunted growth, which became more prominent as they aged, and weigh significantly less than littermates from P8 (p < 0.05). (G) Comparison of mutant and normal thymus from P3 mice. The mutant thymus (left) is dramatically smaller for its age compared to the normal littermate (right). The scale bar equals 1 mm. (H) Skeletal preparations of normal (left) and mutant (right), showing differences in development of both incisor (I) and molar (M) teeth. The
T8169 15250-15257 NN denotes ability
T8170 15299-15303 VBN denotes used
T8171 15258-15260 IN denotes of
T8172 15261-15266 JJ denotes whole
T8173 15267-15274 NNS denotes embryos
T8174 15275-15277 TO denotes to
T8175 15278-15285 VB denotes exclude
T8176 15286-15290 JJ denotes blue
T8177 15291-15294 NN denotes dye
T8178 15295-15298 VBD denotes was
T8179 15304-15306 TO denotes to
T8180 15307-15314 VB denotes examine
T8181 15315-15318 DT denotes the
T8182 15329-15336 NN denotes barrier
T8183 15319-15328 JJ denotes epidermal
T8184 15336-15338 , denotes ,
T8185 15338-15346 RB denotes normally
T8186 15347-15355 VBN denotes acquired
T8187 15356-15365 VBG denotes beginning
T8188 15366-15368 IN denotes at
T8189 15369-15372 NN denotes E16
T8190 15373-15376 CC denotes and
T8191 15377-15385 JJ denotes complete
T8192 15386-15388 IN denotes by
T8193 15389-15394 NN denotes E18.5
T8194 15395-15396 -LRB- denotes [
T8195 15396-15398 CD denotes 21
T8196 15398-15399 -RRB- denotes ]
T8197 15399-15400 . denotes .
T8198 15400-15545 sentence denotes Analyses of E17.5–E18.5 KA mutants showed that they were able to exclude blue dye, indicating that the epidermal barrier was intact (Figure S2).
T8199 15401-15409 NNS denotes Analyses
T8200 15436-15442 VBD denotes showed
T8201 15410-15412 IN denotes of
T8202 15413-15418 NN denotes E17.5
T8203 15428-15435 NNS denotes mutants
T8204 15418-15419 SYM denotes
T8205 15419-15424 NN denotes E18.5
T8206 15425-15427 NN denotes KA
T8207 15443-15447 IN denotes that
T8208 15453-15457 VBD denotes were
T8209 15448-15452 PRP denotes they
T8210 15458-15462 JJ denotes able
T8211 15463-15465 TO denotes to
T8212 15466-15473 VB denotes exclude
T8213 15474-15478 JJ denotes blue
T8214 15479-15482 NN denotes dye
T8215 15482-15484 , denotes ,
T8216 15484-15494 VBG denotes indicating
T8217 15495-15499 IN denotes that
T8218 15522-15525 VBD denotes was
T8219 15500-15503 DT denotes the
T8220 15514-15521 NN denotes barrier
T8221 15504-15513 JJ denotes epidermal
T8222 15526-15532 JJ denotes intact
T8223 15533-15534 -LRB- denotes (
T8224 15541-15543 NN denotes S2
T8225 15534-15540 NN denotes Figure
T8226 15543-15544 -RRB- denotes )
T8227 15544-15545 . denotes .
T8228 15545-15793 sentence denotes At these embryonic ages, there were no differences in size between the mutants and their littermates, but the mutants showed a patch of “birthmark” or dark pigmentation on their foreheads and a dark median line that ran caudally from head to tail.
T8229 15546-15548 IN denotes At
T8230 15577-15581 VBD denotes were
T8231 15549-15554 DT denotes these
T8232 15565-15569 NNS denotes ages
T8233 15555-15564 JJ denotes embryonic
T8234 15569-15571 , denotes ,
T8235 15571-15576 EX denotes there
T8236 15582-15584 DT denotes no
T8237 15585-15596 NNS denotes differences
T8238 15597-15599 IN denotes in
T8239 15600-15604 NN denotes size
T8240 15605-15612 IN denotes between
T8241 15613-15616 DT denotes the
T8242 15617-15624 NNS denotes mutants
T8243 15625-15628 CC denotes and
T8244 15629-15634 PRP$ denotes their
T8245 15635-15646 NNS denotes littermates
T8246 15646-15648 , denotes ,
T8247 15648-15651 CC denotes but
T8248 15652-15655 DT denotes the
T8249 15656-15663 NNS denotes mutants
T8250 15664-15670 VBD denotes showed
T8251 15671-15672 DT denotes a
T8252 15673-15678 NN denotes patch
T8253 15679-15681 IN denotes of
T8254 15682-15683 `` denotes
T8255 15683-15692 NN denotes birthmark
T8256 15692-15693 '' denotes
T8257 15694-15696 CC denotes or
T8258 15697-15701 JJ denotes dark
T8259 15702-15714 NN denotes pigmentation
T8260 15715-15717 IN denotes on
T8261 15718-15723 PRP$ denotes their
T8262 15724-15733 NNS denotes foreheads
T8263 15734-15737 CC denotes and
T8264 15738-15739 DT denotes a
T8265 15752-15756 NN denotes line
T8266 15740-15744 JJ denotes dark
T8267 15745-15751 JJ denotes median
T8268 15757-15761 WDT denotes that
T8269 15762-15765 VBD denotes ran
T8270 15766-15774 RB denotes caudally
T8271 15775-15779 IN denotes from
T8272 15780-15784 NN denotes head
T8273 15785-15787 IN denotes to
T8274 15788-15792 NN denotes tail
T8275 15792-15793 . denotes .
T8276 15793-15900 sentence denotes Their external ears or pinnae were shriveled in appearance and pigmented compared to those of littermates.
T8277 15794-15799 PRP$ denotes Their
T8278 15809-15813 NNS denotes ears
T8279 15800-15808 JJ denotes external
T8280 15824-15828 VBD denotes were
T8281 15814-15816 CC denotes or
T8282 15817-15823 NNS denotes pinnae
T8283 15829-15838 JJ denotes shriveled
T8284 15839-15841 IN denotes in
T8285 15842-15852 NN denotes appearance
T8286 15853-15856 CC denotes and
T8287 15857-15866 JJ denotes pigmented
T8288 15867-15875 VBN denotes compared
T8289 15876-15878 IN denotes to
T8290 15879-15884 DT denotes those
T8291 15885-15887 IN denotes of
T8292 15888-15899 NNS denotes littermates
T8293 15899-15900 . denotes .
T8294 15900-16043 sentence denotes External characteristics of KA mutants that were evident at E18.5 persisted after birth and became more prominent as they grew (Figure 2A–2F).
T8295 15901-15909 JJ denotes External
T8296 15910-15925 NNS denotes characteristics
T8297 15967-15976 VBD denotes persisted
T8298 15926-15928 IN denotes of
T8299 15929-15931 NN denotes KA
T8300 15932-15939 NNS denotes mutants
T8301 15940-15944 WDT denotes that
T8302 15945-15949 VBD denotes were
T8303 15950-15957 JJ denotes evident
T8304 15958-15960 IN denotes at
T8305 15961-15966 NN denotes E18.5
T8306 15977-15982 IN denotes after
T8307 15983-15988 NN denotes birth
T8308 15989-15992 CC denotes and
T8309 15993-15999 VBD denotes became
T8310 16000-16004 RBR denotes more
T8311 16005-16014 JJ denotes prominent
T8312 16015-16017 IN denotes as
T8313 16023-16027 VBD denotes grew
T8314 16018-16022 PRP denotes they
T8315 16028-16029 -LRB- denotes (
T8316 16036-16038 NN denotes 2A
T8317 16029-16035 NN denotes Figure
T8318 16038-16039 SYM denotes
T8319 16039-16041 NN denotes 2F
T8320 16041-16042 -RRB- denotes )
T8321 16042-16043 . denotes .
T8322 16043-16103 sentence denotes Growth of pelage hair was generally delayed in the mutants.
T8323 16044-16050 NN denotes Growth
T8324 16080-16087 VBN denotes delayed
T8325 16051-16053 IN denotes of
T8326 16054-16060 NN denotes pelage
T8327 16061-16065 NN denotes hair
T8328 16066-16069 VBD denotes was
T8329 16070-16079 RB denotes generally
T8330 16088-16090 IN denotes in
T8331 16091-16094 DT denotes the
T8332 16095-16102 NNS denotes mutants
T8333 16102-16103 . denotes .
T8334 16103-16258 sentence denotes At around P8, the KA mutants were hairless and had wrinkled skin while their phenotypically normal littermates had a smooth thin coat of hair (Figure 2B).
T8335 16104-16106 IN denotes At
T8336 16133-16137 VBD denotes were
T8337 16107-16113 RB denotes around
T8338 16114-16116 NN denotes P8
T8339 16116-16118 , denotes ,
T8340 16118-16121 DT denotes the
T8341 16125-16132 NNS denotes mutants
T8342 16122-16124 NN denotes KA
T8343 16138-16146 JJ denotes hairless
T8344 16147-16150 CC denotes and
T8345 16151-16154 VBD denotes had
T8346 16155-16163 VBN denotes wrinkled
T8347 16164-16168 NN denotes skin
T8348 16169-16174 IN denotes while
T8349 16215-16218 VBD denotes had
T8350 16175-16180 PRP$ denotes their
T8351 16203-16214 NNS denotes littermates
T8352 16181-16195 RB denotes phenotypically
T8353 16196-16202 JJ denotes normal
T8354 16219-16220 DT denotes a
T8355 16233-16237 NN denotes coat
T8356 16221-16227 JJ denotes smooth
T8357 16228-16232 JJ denotes thin
T8358 16238-16240 IN denotes of
T8359 16241-16245 NN denotes hair
T8360 16246-16247 -LRB- denotes (
T8361 16254-16256 NN denotes 2B
T8362 16247-16253 NN denotes Figure
T8363 16256-16257 -RRB- denotes )
T8364 16257-16258 . denotes .
T8365 16258-16387 sentence denotes At this age, two lower incisors start to erupt in normal littermates and these were absent in the KA mutants (Figure 2C and 2D).
T8366 16259-16261 IN denotes At
T8367 16291-16296 VBP denotes start
T8368 16262-16266 DT denotes this
T8369 16267-16270 NN denotes age
T8370 16270-16272 , denotes ,
T8371 16272-16275 CD denotes two
T8372 16282-16290 NNS denotes incisors
T8373 16276-16281 JJR denotes lower
T8374 16297-16299 TO denotes to
T8375 16300-16305 VB denotes erupt
T8376 16306-16308 IN denotes in
T8377 16309-16315 JJ denotes normal
T8378 16316-16327 NNS denotes littermates
T8379 16328-16331 CC denotes and
T8380 16332-16337 DT denotes these
T8381 16338-16342 VBD denotes were
T8382 16343-16349 JJ denotes absent
T8383 16350-16352 IN denotes in
T8384 16353-16356 DT denotes the
T8385 16360-16367 NNS denotes mutants
T8386 16357-16359 NN denotes KA
T8387 16368-16369 -LRB- denotes (
T8388 16376-16378 NN denotes 2C
T8389 16369-16375 NN denotes Figure
T8390 16379-16382 CC denotes and
T8391 16383-16385 NN denotes 2D
T8392 16385-16386 -RRB- denotes )
T8393 16386-16387 . denotes .
T8394 16387-16542 sentence denotes Animals also tended to be smaller and around P10–P12 displayed abnormally short and misshapen vibrissae and short, shaggy pelage hairs (Figure 2C and 2D).
T8395 16388-16395 NNS denotes Animals
T8396 16401-16407 VBD denotes tended
T8397 16396-16400 RB denotes also
T8398 16408-16410 TO denotes to
T8399 16411-16413 VB denotes be
T8400 16414-16421 JJR denotes smaller
T8401 16422-16425 CC denotes and
T8402 16426-16432 IN denotes around
T8403 16441-16450 VBD denotes displayed
T8404 16433-16436 NN denotes P10
T8405 16436-16437 SYM denotes
T8406 16437-16440 NN denotes P12
T8407 16451-16461 RB denotes abnormally
T8408 16462-16467 JJ denotes short
T8409 16482-16491 NNS denotes vibrissae
T8410 16468-16471 CC denotes and
T8411 16472-16481 JJ denotes misshapen
T8412 16492-16495 CC denotes and
T8413 16496-16501 JJ denotes short
T8414 16517-16522 NNS denotes hairs
T8415 16501-16503 , denotes ,
T8416 16503-16509 JJ denotes shaggy
T8417 16510-16516 NN denotes pelage
T8418 16523-16524 -LRB- denotes (
T8419 16531-16533 NN denotes 2C
T8420 16524-16530 NN denotes Figure
T8421 16534-16537 CC denotes and
T8422 16538-16540 NN denotes 2D
T8423 16540-16541 -RRB- denotes )
T8424 16541-16542 . denotes .
T8425 16542-16681 sentence denotes Development of thick ridges in their skin, particularly around the ears, eyelids, forehead, nose, and paws, became noticeable (Figure 2E).
T8426 16543-16554 NN denotes Development
T8427 16651-16657 VBD denotes became
T8428 16555-16557 IN denotes of
T8429 16558-16563 JJ denotes thick
T8430 16564-16570 NNS denotes ridges
T8431 16571-16573 IN denotes in
T8432 16574-16579 PRP$ denotes their
T8433 16580-16584 NN denotes skin
T8434 16584-16586 , denotes ,
T8435 16586-16598 RB denotes particularly
T8436 16599-16605 IN denotes around
T8437 16606-16609 DT denotes the
T8438 16610-16614 NNS denotes ears
T8439 16614-16616 , denotes ,
T8440 16616-16623 NNS denotes eyelids
T8441 16623-16625 , denotes ,
T8442 16625-16633 NN denotes forehead
T8443 16633-16635 , denotes ,
T8444 16635-16639 NN denotes nose
T8445 16639-16641 , denotes ,
T8446 16641-16644 CC denotes and
T8447 16645-16649 NNS denotes paws
T8448 16649-16651 , denotes ,
T8449 16658-16668 JJ denotes noticeable
T8450 16669-16670 -LRB- denotes (
T8451 16677-16679 NN denotes 2E
T8452 16670-16676 NN denotes Figure
T8453 16679-16680 -RRB- denotes )
T8454 16680-16681 . denotes .
T8455 16681-16756 sentence denotes These regions looked scaly, and these animals hardly kept their eyes open.
T8456 16682-16687 DT denotes These
T8457 16688-16695 NNS denotes regions
T8458 16696-16702 VBD denotes looked
T8459 16703-16708 JJ denotes scaly
T8460 16708-16710 , denotes ,
T8461 16710-16713 CC denotes and
T8462 16714-16719 DT denotes these
T8463 16720-16727 NNS denotes animals
T8464 16735-16739 VBD denotes kept
T8465 16728-16734 RB denotes hardly
T8466 16740-16745 PRP$ denotes their
T8467 16746-16750 NNS denotes eyes
T8468 16751-16755 JJ denotes open
T8469 16755-16756 . denotes .
T8470 16756-17005 sentence denotes In contrast to the normal littermates that consistently increased their body weight with age, surviving KA mutants started to lose weight from P10 onwards; by P16–P17 they were all lethargic, and none of them survived to weaning (Figure 2E and 2F).
T8471 16757-16759 IN denotes In
T8472 16872-16879 VBD denotes started
T8473 16760-16768 NN denotes contrast
T8474 16769-16771 IN denotes to
T8475 16772-16775 DT denotes the
T8476 16783-16794 NNS denotes littermates
T8477 16776-16782 JJ denotes normal
T8478 16795-16799 WDT denotes that
T8479 16813-16822 VBD denotes increased
T8480 16800-16812 RB denotes consistently
T8481 16823-16828 PRP$ denotes their
T8482 16834-16840 NN denotes weight
T8483 16829-16833 NN denotes body
T8484 16841-16845 IN denotes with
T8485 16846-16849 NN denotes age
T8486 16849-16851 , denotes ,
T8487 16851-16860 VBG denotes surviving
T8488 16864-16871 NNS denotes mutants
T8489 16861-16863 NN denotes KA
T8490 16929-16933 VBD denotes were
T8491 16880-16882 TO denotes to
T8492 16883-16887 VB denotes lose
T8493 16888-16894 NN denotes weight
T8494 16895-16899 IN denotes from
T8495 16900-16903 NN denotes P10
T8496 16904-16911 RB denotes onwards
T8497 16911-16912 : denotes ;
T8498 16913-16915 IN denotes by
T8499 16916-16919 NN denotes P16
T8500 16919-16920 SYM denotes
T8501 16920-16923 NN denotes P17
T8502 16924-16928 PRP denotes they
T8503 16934-16937 RB denotes all
T8504 16938-16947 JJ denotes lethargic
T8505 16947-16949 , denotes ,
T8506 16949-16952 CC denotes and
T8507 16953-16957 NN denotes none
T8508 16966-16974 VBD denotes survived
T8509 16958-16960 IN denotes of
T8510 16961-16965 PRP denotes them
T8511 16975-16977 IN denotes to
T8512 16978-16985 NN denotes weaning
T8513 16986-16987 -LRB- denotes (
T8514 16994-16996 NN denotes 2E
T8515 16987-16993 NN denotes Figure
T8516 16997-17000 CC denotes and
T8517 17001-17003 NN denotes 2F
T8518 17003-17004 -RRB- denotes )
T8519 17004-17005 . denotes .
T8520 17005-17298 sentence denotes At the time of autopsy all the mutants were toothless, without incisors or molars, and their stomachs were consistently small and had no solid food, unlike their age-matched littermates, suggesting that the observed weight loss could be the result of failure to ingest solid food (Figure 2F).
T8521 17006-17008 IN denotes At
T8522 17045-17049 VBD denotes were
T8523 17009-17012 DT denotes the
T8524 17013-17017 NN denotes time
T8525 17018-17020 IN denotes of
T8526 17021-17028 NN denotes autopsy
T8527 17029-17032 PDT denotes all
T8528 17037-17044 NNS denotes mutants
T8529 17033-17036 DT denotes the
T8530 17050-17059 JJ denotes toothless
T8531 17059-17061 , denotes ,
T8532 17061-17068 IN denotes without
T8533 17069-17077 NNS denotes incisors
T8534 17078-17080 CC denotes or
T8535 17081-17087 NNS denotes molars
T8536 17087-17089 , denotes ,
T8537 17089-17092 CC denotes and
T8538 17093-17098 PRP$ denotes their
T8539 17099-17107 NNS denotes stomachs
T8540 17108-17112 VBD denotes were
T8541 17113-17125 RB denotes consistently
T8542 17126-17131 JJ denotes small
T8543 17132-17135 CC denotes and
T8544 17136-17139 VBD denotes had
T8545 17140-17142 DT denotes no
T8546 17149-17153 NN denotes food
T8547 17143-17148 JJ denotes solid
T8548 17153-17155 , denotes ,
T8549 17155-17161 IN denotes unlike
T8550 17162-17167 PRP$ denotes their
T8551 17180-17191 NNS denotes littermates
T8552 17168-17171 NN denotes age
T8553 17172-17179 JJ denotes matched
T8554 17171-17172 HYPH denotes -
T8555 17191-17193 , denotes ,
T8556 17193-17203 VBG denotes suggesting
T8557 17204-17208 IN denotes that
T8558 17240-17242 VB denotes be
T8559 17209-17212 DT denotes the
T8560 17229-17233 NN denotes loss
T8561 17213-17221 VBN denotes observed
T8562 17222-17228 NN denotes weight
T8563 17234-17239 MD denotes could
T8564 17243-17246 DT denotes the
T8565 17247-17253 NN denotes result
T8566 17254-17256 IN denotes of
T8567 17257-17264 NN denotes failure
T8568 17265-17267 TO denotes to
T8569 17268-17274 VB denotes ingest
T8570 17275-17280 JJ denotes solid
T8571 17281-17285 NN denotes food
T8572 17286-17287 -LRB- denotes (
T8573 17294-17296 NN denotes 2F
T8574 17287-17293 NN denotes Figure
T8575 17296-17297 -RRB- denotes )
T8576 17297-17298 . denotes .
T8577 17298-17514 sentence denotes Interestingly, changes in body weights and timing of hair growth varied considerably among mutant pups even if they were from the same litter, whereas those of phenotypically normal littermates tended to be similar.
T8578 17299-17312 RB denotes Interestingly
T8579 17364-17370 VBD denotes varied
T8580 17312-17314 , denotes ,
T8581 17314-17321 NNS denotes changes
T8582 17322-17324 IN denotes in
T8583 17325-17329 NN denotes body
T8584 17330-17337 NNS denotes weights
T8585 17338-17341 CC denotes and
T8586 17342-17348 NN denotes timing
T8587 17349-17351 IN denotes of
T8588 17352-17356 NN denotes hair
T8589 17357-17363 NN denotes growth
T8590 17371-17383 RB denotes considerably
T8591 17384-17389 IN denotes among
T8592 17390-17396 JJ denotes mutant
T8593 17397-17401 NNS denotes pups
T8594 17402-17406 RB denotes even
T8595 17415-17419 VBD denotes were
T8596 17407-17409 IN denotes if
T8597 17410-17414 PRP denotes they
T8598 17420-17424 IN denotes from
T8599 17425-17428 DT denotes the
T8600 17434-17440 NN denotes litter
T8601 17429-17433 JJ denotes same
T8602 17440-17442 , denotes ,
T8603 17442-17449 IN denotes whereas
T8604 17493-17499 VBD denotes tended
T8605 17450-17455 DT denotes those
T8606 17456-17458 IN denotes of
T8607 17459-17473 RB denotes phenotypically
T8608 17474-17480 JJ denotes normal
T8609 17481-17492 NNS denotes littermates
T8610 17500-17502 TO denotes to
T8611 17503-17505 VB denotes be
T8612 17506-17513 JJ denotes similar
T8613 17513-17514 . denotes .
T8614 17514-17700 sentence denotes This difference was also reflected in the variation in timing of death in mutants: some mutant pups were born alive but died within a day or two, some survived close to the weaning age.
T8615 17515-17519 DT denotes This
T8616 17520-17530 NN denotes difference
T8617 17540-17549 VBN denotes reflected
T8618 17531-17534 VBD denotes was
T8619 17535-17539 RB denotes also
T8620 17666-17674 VBD denotes survived
T8621 17550-17552 IN denotes in
T8622 17553-17556 DT denotes the
T8623 17557-17566 NN denotes variation
T8624 17567-17569 IN denotes in
T8625 17570-17576 NN denotes timing
T8626 17577-17579 IN denotes of
T8627 17580-17585 NN denotes death
T8628 17586-17588 IN denotes in
T8629 17589-17596 NNS denotes mutants
T8630 17596-17598 : denotes :
T8631 17598-17602 DT denotes some
T8632 17610-17614 NNS denotes pups
T8633 17603-17609 JJ denotes mutant
T8634 17620-17624 VBN denotes born
T8635 17615-17619 VBD denotes were
T8636 17625-17630 JJ denotes alive
T8637 17631-17634 CC denotes but
T8638 17635-17639 VBD denotes died
T8639 17640-17646 IN denotes within
T8640 17647-17648 DT denotes a
T8641 17649-17652 NN denotes day
T8642 17653-17655 CC denotes or
T8643 17656-17659 CD denotes two
T8644 17659-17661 , denotes ,
T8645 17661-17665 DT denotes some
T8646 17675-17680 RB denotes close
T8647 17681-17683 IN denotes to
T8648 17684-17687 DT denotes the
T8649 17696-17699 NN denotes age
T8650 17688-17695 JJ denotes weaning
T8651 17699-17700 . denotes .
T8652 17700-17829 sentence denotes This variability of the mutant phenotypes suggests possible variation in the timing and efficiency of cre-mediated Apc deletion.
T8653 17701-17705 DT denotes This
T8654 17706-17717 NN denotes variability
T8655 17743-17751 VBZ denotes suggests
T8656 17718-17720 IN denotes of
T8657 17721-17724 DT denotes the
T8658 17732-17742 NNS denotes phenotypes
T8659 17725-17731 JJ denotes mutant
T8660 17752-17760 JJ denotes possible
T8661 17761-17770 NN denotes variation
T8662 17771-17773 IN denotes in
T8663 17774-17777 DT denotes the
T8664 17778-17784 NN denotes timing
T8665 17785-17788 CC denotes and
T8666 17789-17799 NN denotes efficiency
T8667 17800-17802 IN denotes of
T8668 17803-17806 NN denotes cre
T8669 17807-17815 JJ denotes mediated
T8670 17806-17807 HYPH denotes -
T8671 17820-17828 NN denotes deletion
T8672 17816-17819 NN denotes Apc
T8673 17828-17829 . denotes .
T8674 17829-17912 sentence denotes It is possible that the genetic background has a role to play in this variability.
T8675 17830-17832 PRP denotes It
T8676 17833-17835 VBZ denotes is
T8677 17836-17844 JJ denotes possible
T8678 17845-17849 IN denotes that
T8679 17873-17876 VBZ denotes has
T8680 17850-17853 DT denotes the
T8681 17862-17872 NN denotes background
T8682 17854-17861 JJ denotes genetic
T8683 17877-17878 DT denotes a
T8684 17879-17883 NN denotes role
T8685 17884-17886 TO denotes to
T8686 17887-17891 VB denotes play
T8687 17892-17894 IN denotes in
T8688 17895-17899 DT denotes this
T8689 17900-17911 NN denotes variability
T8690 17911-17912 . denotes .
T8691 17912-18128 sentence denotes Gross examination of internal organs also showed that the mutants' thymi were consistently inconspicuous and were very small for their age, whereas those of their littermates were very prominent in size (Figure 2G).
T8692 17913-17918 JJ denotes Gross
T8693 17919-17930 NN denotes examination
T8694 17955-17961 VBD denotes showed
T8695 17931-17933 IN denotes of
T8696 17934-17942 JJ denotes internal
T8697 17943-17949 NNS denotes organs
T8698 17950-17954 RB denotes also
T8699 17962-17966 IN denotes that
T8700 17986-17990 VBD denotes were
T8701 17967-17970 DT denotes the
T8702 17971-17978 NNS denotes mutants
T8703 17980-17985 NNS denotes thymi
T8704 17978-17979 POS denotes '
T8705 17991-18003 RB denotes consistently
T8706 18004-18017 JJ denotes inconspicuous
T8707 18018-18021 CC denotes and
T8708 18022-18026 VBD denotes were
T8709 18027-18031 RB denotes very
T8710 18032-18037 JJ denotes small
T8711 18038-18041 IN denotes for
T8712 18042-18047 PRP$ denotes their
T8713 18048-18051 NN denotes age
T8714 18051-18053 , denotes ,
T8715 18053-18060 IN denotes whereas
T8716 18088-18092 VBD denotes were
T8717 18061-18066 DT denotes those
T8718 18067-18069 IN denotes of
T8719 18070-18075 PRP$ denotes their
T8720 18076-18087 NNS denotes littermates
T8721 18093-18097 RB denotes very
T8722 18098-18107 JJ denotes prominent
T8723 18108-18110 IN denotes in
T8724 18111-18115 NN denotes size
T8725 18116-18117 -LRB- denotes (
T8726 18124-18126 NN denotes 2G
T8727 18117-18123 NN denotes Figure
T8728 18126-18127 -RRB- denotes )
T8729 18127-18128 . denotes .
T8730 18128-18172 sentence denotes This difference was evident as early as P3.
T8731 18129-18133 DT denotes This
T8732 18134-18144 NN denotes difference
T8733 18145-18148 VBD denotes was
T8734 18149-18156 JJ denotes evident
T8735 18157-18159 RB denotes as
T8736 18160-18165 RB denotes early
T8737 18166-18168 IN denotes as
T8738 18169-18171 NN denotes P3
T8739 18171-18172 . denotes .
T8740 18172-18293 sentence denotes Quite frequently mutant thymi in P12–P17 mutant mice also contained black deposits within the tissue (unpublished data).
T8741 18173-18178 RB denotes Quite
T8742 18179-18189 RB denotes frequently
T8743 18231-18240 VBD denotes contained
T8744 18190-18196 JJ denotes mutant
T8745 18197-18202 NNS denotes thymi
T8746 18203-18205 IN denotes in
T8747 18206-18209 NN denotes P12
T8748 18221-18225 NNS denotes mice
T8749 18209-18210 SYM denotes
T8750 18210-18213 NN denotes P17
T8751 18214-18220 JJ denotes mutant
T8752 18226-18230 RB denotes also
T8753 18241-18246 JJ denotes black
T8754 18247-18255 NNS denotes deposits
T8755 18256-18262 IN denotes within
T8756 18263-18266 DT denotes the
T8757 18267-18273 NN denotes tissue
T8758 18274-18275 -LRB- denotes (
T8759 18287-18291 NNS denotes data
T8760 18275-18286 JJ denotes unpublished
T8761 18291-18292 -RRB- denotes )
T8762 18292-18293 . denotes .
T8763 18293-18430 sentence denotes Mutant mice were also examined for any skeletal abnormalities by preparing skeletal specimens of P16–P17 mice stained with Alizarin red.
T8764 18294-18300 JJ denotes Mutant
T8765 18301-18305 NNS denotes mice
T8766 18316-18324 VBN denotes examined
T8767 18306-18310 VBD denotes were
T8768 18311-18315 RB denotes also
T8769 18325-18328 IN denotes for
T8770 18329-18332 DT denotes any
T8771 18342-18355 NNS denotes abnormalities
T8772 18333-18341 JJ denotes skeletal
T8773 18356-18358 IN denotes by
T8774 18359-18368 VBG denotes preparing
T8775 18369-18377 JJ denotes skeletal
T8776 18378-18387 NNS denotes specimens
T8777 18388-18390 IN denotes of
T8778 18391-18394 NN denotes P16
T8779 18399-18403 NNS denotes mice
T8780 18394-18395 SYM denotes
T8781 18395-18398 NN denotes P17
T8782 18404-18411 VBN denotes stained
T8783 18412-18416 IN denotes with
T8784 18417-18425 NN denotes Alizarin
T8785 18426-18429 NN denotes red
T8786 18429-18430 . denotes .
T8787 18430-18622 sentence denotes No differences between the normal and KA mutant mice in the mandibular bone can be detected, but the mutant mice lacked or had underdeveloped set of maxillary incisors and molars (Figure 2H).
T8788 18431-18433 DT denotes No
T8789 18434-18445 NNS denotes differences
T8790 18514-18522 VBN denotes detected
T8791 18446-18453 IN denotes between
T8792 18454-18457 DT denotes the
T8793 18479-18483 NNS denotes mice
T8794 18458-18464 JJ denotes normal
T8795 18465-18468 CC denotes and
T8796 18469-18471 NN denotes KA
T8797 18472-18478 JJ denotes mutant
T8798 18484-18486 IN denotes in
T8799 18487-18490 DT denotes the
T8800 18502-18506 NN denotes bone
T8801 18491-18501 JJ denotes mandibular
T8802 18507-18510 MD denotes can
T8803 18511-18513 VB denotes be
T8804 18522-18524 , denotes ,
T8805 18524-18527 CC denotes but
T8806 18528-18531 DT denotes the
T8807 18539-18543 NNS denotes mice
T8808 18532-18538 JJ denotes mutant
T8809 18544-18550 VBD denotes lacked
T8810 18551-18553 CC denotes or
T8811 18554-18557 VBD denotes had
T8812 18558-18572 VBN denotes underdeveloped
T8813 18573-18576 NN denotes set
T8814 18577-18579 IN denotes of
T8815 18580-18589 JJ denotes maxillary
T8816 18590-18598 NNS denotes incisors
T8817 18599-18602 CC denotes and
T8818 18603-18609 NNS denotes molars
T8819 18610-18611 -LRB- denotes (
T8820 18618-18620 NN denotes 2H
T8821 18611-18617 NN denotes Figure
T8822 18620-18621 -RRB- denotes )
T8823 18621-18622 . denotes .
T8824 18622-18673 sentence denotes We detected no other major skeletal abnormalities.
T8825 18623-18625 PRP denotes We
T8826 18626-18634 VBD denotes detected
T8827 18635-18637 DT denotes no
T8828 18659-18672 NNS denotes abnormalities
T8829 18638-18643 JJ denotes other
T8830 18644-18649 JJ denotes major
T8831 18650-18658 JJ denotes skeletal
T8832 18672-18673 . denotes .
T9640 18852-18859 VBN denotes deleted
T9607 18675-18683 NN denotes Genotype
T9608 18696-18704 JJ denotes Specific
T9609 18683-18684 HYPH denotes -
T9610 18685-18688 CC denotes and
T9611 18689-18695 NN denotes Tissue
T9612 18695-18696 HYPH denotes -
T9613 18705-18715 NN denotes Expression
T9614 18716-18718 IN denotes of
T9615 18719-18722 DT denotes the
T9616 18737-18748 NNS denotes Transcripts
T9617 18723-18732 VBN denotes Truncated
T9618 18733-18736 NN denotes Apc
T9619 18748-18882 sentence denotes To assess the molecular effects of the K14-cre–mediated recombination, we screened for the presence of deleted Apc (ApcΔ580) alleles.
T9620 18749-18751 TO denotes To
T9621 18752-18758 VB denotes assess
T9622 18823-18831 VBD denotes screened
T9623 18759-18762 DT denotes the
T9624 18773-18780 NNS denotes effects
T9625 18763-18772 JJ denotes molecular
T9626 18781-18783 IN denotes of
T9627 18784-18787 DT denotes the
T9628 18805-18818 NN denotes recombination
T9629 18788-18791 NN denotes K14
T9630 18792-18795 NN denotes cre
T9631 18791-18792 HYPH denotes -
T9632 18796-18804 JJ denotes mediated
T9633 18795-18796 HYPH denotes
T9634 18818-18820 , denotes ,
T9635 18820-18822 PRP denotes we
T9636 18832-18835 IN denotes for
T9637 18836-18839 DT denotes the
T9638 18840-18848 NN denotes presence
T9639 18849-18851 IN denotes of
T9641 18860-18863 NN denotes Apc
T9642 18874-18881 NNS denotes alleles
T9643 18864-18865 -LRB- denotes (
T9644 18865-18872 NN denotes ApcΔ580
T9645 18872-18873 -RRB- denotes )
T9646 18881-18882 . denotes .
T9647 18882-19034 sentence denotes Genomic DNA was extracted from liver, thymus, and skin from all 4 possible genotypes: K14-cre; ApcCKO/CKO, K14-cre; ApcCKO/+, ApcCKO/CKO, and ApcCKO/+.
T9648 18883-18890 JJ denotes Genomic
T9649 18891-18894 NN denotes DNA
T9650 18899-18908 VBN denotes extracted
T9651 18895-18898 VBD denotes was
T9652 18909-18913 IN denotes from
T9653 18914-18919 NN denotes liver
T9654 18919-18921 , denotes ,
T9655 18921-18927 NN denotes thymus
T9656 18927-18929 , denotes ,
T9657 18929-18932 CC denotes and
T9658 18933-18937 NN denotes skin
T9659 18938-18942 IN denotes from
T9660 18943-18946 DT denotes all
T9661 18958-18967 NNS denotes genotypes
T9662 18947-18948 CD denotes 4
T9663 18949-18957 JJ denotes possible
T9664 18967-18969 : denotes :
T9665 18969-18972 NN denotes K14
T9666 18973-18976 NN denotes cre
T9667 18972-18973 HYPH denotes -
T9668 18976-18977 : denotes ;
T9669 18978-18984 NN denotes ApcCKO
T9670 18985-18988 NN denotes CKO
T9671 18984-18985 HYPH denotes /
T9672 18988-18990 , denotes ,
T9673 18990-18993 NN denotes K14
T9674 18994-18997 NN denotes cre
T9675 18993-18994 HYPH denotes -
T9676 18997-18998 : denotes ;
T9677 18999-19005 NN denotes ApcCKO
T9678 19005-19006 HYPH denotes /
T9679 19006-19007 SYM denotes +
T9680 19007-19009 , denotes ,
T9681 19009-19015 NN denotes ApcCKO
T9682 19016-19019 NN denotes CKO
T9683 19015-19016 HYPH denotes /
T9684 19019-19021 , denotes ,
T9685 19021-19024 CC denotes and
T9686 19025-19031 NN denotes ApcCKO
T9687 19031-19032 HYPH denotes /
T9688 19032-19033 SYM denotes +
T9689 19033-19034 . denotes .
T9690 19034-19200 sentence denotes Genotyping on genomic DNA from these tissues showed that the ApcΔ580 allele (500-bp product) was detected only from the skin and thymus of the K14-cre–positive mice.
T9691 19035-19045 VBG denotes Genotyping
T9692 19080-19086 VBD denotes showed
T9693 19046-19048 IN denotes on
T9694 19049-19056 JJ denotes genomic
T9695 19057-19060 NN denotes DNA
T9696 19061-19065 IN denotes from
T9697 19066-19071 DT denotes these
T9698 19072-19079 NNS denotes tissues
T9699 19087-19091 IN denotes that
T9700 19132-19140 VBN denotes detected
T9701 19092-19095 DT denotes the
T9702 19104-19110 NN denotes allele
T9703 19096-19103 NN denotes ApcΔ580
T9704 19111-19112 -LRB- denotes (
T9705 19119-19126 NN denotes product
T9706 19112-19115 CD denotes 500
T9707 19116-19118 NN denotes bp
T9708 19115-19116 HYPH denotes -
T9709 19126-19127 -RRB- denotes )
T9710 19128-19131 VBD denotes was
T9711 19141-19145 RB denotes only
T9712 19146-19150 IN denotes from
T9713 19151-19154 DT denotes the
T9714 19155-19159 NN denotes skin
T9715 19160-19163 CC denotes and
T9716 19164-19170 NN denotes thymus
T9717 19171-19173 IN denotes of
T9718 19174-19177 DT denotes the
T9719 19195-19199 NNS denotes mice
T9720 19178-19181 NN denotes K14
T9721 19182-19185 NN denotes cre
T9722 19181-19182 HYPH denotes -
T9723 19186-19194 JJ denotes positive
T9724 19185-19186 HYPH denotes
T9725 19199-19200 . denotes .
T9726 19200-19385 sentence denotes The presence of mutant Apc allele in the thymus of K14-cre; ApcCKO/+ mice was consistently much less than the DNA from the skin of the same animal or other tissues from the KA mutants.
T9727 19201-19204 DT denotes The
T9728 19205-19213 NN denotes presence
T9729 19275-19278 VBD denotes was
T9730 19214-19216 IN denotes of
T9731 19217-19223 JJ denotes mutant
T9732 19228-19234 NN denotes allele
T9733 19224-19227 NN denotes Apc
T9734 19235-19237 IN denotes in
T9735 19238-19241 DT denotes the
T9736 19242-19248 NN denotes thymus
T9737 19249-19251 IN denotes of
T9738 19252-19255 NN denotes K14
T9739 19256-19259 NN denotes cre
T9740 19255-19256 HYPH denotes -
T9741 19270-19274 NNS denotes mice
T9742 19259-19260 : denotes ;
T9743 19261-19267 NN denotes ApcCKO
T9744 19267-19268 HYPH denotes /
T9745 19268-19269 SYM denotes +
T9746 19279-19291 RB denotes consistently
T9747 19292-19296 RB denotes much
T9748 19297-19301 JJR denotes less
T9749 19302-19306 IN denotes than
T9750 19307-19310 DT denotes the
T9751 19311-19314 NN denotes DNA
T9752 19315-19319 IN denotes from
T9753 19320-19323 DT denotes the
T9754 19324-19328 NN denotes skin
T9755 19329-19331 IN denotes of
T9756 19332-19335 DT denotes the
T9757 19341-19347 NN denotes animal
T9758 19336-19340 JJ denotes same
T9759 19348-19350 CC denotes or
T9760 19351-19356 JJ denotes other
T9761 19357-19364 NNS denotes tissues
T9762 19365-19369 IN denotes from
T9763 19370-19373 DT denotes the
T9764 19377-19384 NNS denotes mutants
T9765 19374-19376 NN denotes KA
T9766 19384-19385 . denotes .
T9767 19385-19671 sentence denotes In addition, this product was not detected at all in either the liver of K14-cre–positive or in any of the K14-cre–negative mouse tissues samples, establishing that Cre-mediated recombination has taken place in the tissue-specific manner in the mice that inherited K14-cre (Figure 3A).
T9768 19386-19388 IN denotes In
T9769 19420-19428 VBN denotes detected
T9770 19389-19397 NN denotes addition
T9771 19397-19399 , denotes ,
T9772 19399-19403 DT denotes this
T9773 19404-19411 NN denotes product
T9774 19412-19415 VBD denotes was
T9775 19416-19419 RB denotes not
T9776 19429-19431 RB denotes at
T9777 19432-19435 RB denotes all
T9778 19436-19438 IN denotes in
T9779 19439-19445 CC denotes either
T9780 19450-19455 NN denotes liver
T9781 19446-19449 DT denotes the
T9782 19456-19458 IN denotes of
T9783 19459-19462 NN denotes K14
T9784 19463-19466 NN denotes cre
T9785 19462-19463 HYPH denotes -
T9786 19467-19475 JJ denotes positive
T9787 19466-19467 HYPH denotes
T9788 19476-19478 CC denotes or
T9789 19479-19481 IN denotes in
T9790 19482-19485 DT denotes any
T9791 19486-19488 IN denotes of
T9792 19489-19492 DT denotes the
T9793 19501-19509 JJ denotes negative
T9794 19493-19496 NN denotes K14
T9795 19497-19500 NN denotes cre
T9796 19496-19497 HYPH denotes -
T9797 19500-19501 HYPH denotes
T9798 19510-19515 NN denotes mouse
T9799 19524-19531 NNS denotes samples
T9800 19516-19523 NNS denotes tissues
T9801 19531-19533 , denotes ,
T9802 19533-19545 VBG denotes establishing
T9803 19546-19550 IN denotes that
T9804 19582-19587 VBN denotes taken
T9805 19551-19554 NN denotes Cre
T9806 19555-19563 JJ denotes mediated
T9807 19554-19555 HYPH denotes -
T9808 19564-19577 NN denotes recombination
T9809 19578-19581 VBZ denotes has
T9810 19588-19593 NN denotes place
T9811 19594-19596 IN denotes in
T9812 19597-19600 DT denotes the
T9813 19617-19623 NN denotes manner
T9814 19601-19607 NN denotes tissue
T9815 19608-19616 JJ denotes specific
T9816 19607-19608 HYPH denotes -
T9817 19624-19626 IN denotes in
T9818 19627-19630 DT denotes the
T9819 19631-19635 NNS denotes mice
T9820 19636-19640 WDT denotes that
T9821 19641-19650 VBD denotes inherited
T9822 19651-19654 NN denotes K14
T9823 19655-19658 NN denotes cre
T9824 19654-19655 HYPH denotes -
T9825 19659-19660 -LRB- denotes (
T9826 19667-19669 NN denotes 3A
T9827 19660-19666 NN denotes Figure
T9828 19669-19670 -RRB- denotes )
T9829 19670-19671 . denotes .
T9830 19671-20393 sentence denotes Figure 3 Tissue-Specific Detection and Expression of Deleted Apc Alleles (A) Tissue-specific genotyping PCR. Only genomic DNA samples from the skin (S) and thymus (T), but not liver (L) of mice positive for K14-cre show the presence of deleted ApcΔ580 allele. (B) Genotype- and tissue-specific expression of the truncated Apc transcripts. A representative gel of RT-PCR using primers F546 and R721, showing that only RNA from the skin and thymus but not liver of mice positive for K14-cre have transcripts from both wild-type (528 bp) and deleted (313 bp) Apc alleles. Apc transcripts were also analyzed by RT-PCR with primers spanning exon 14 (Figure 1A) using total RNA isolated from the corresponding tissue samples.
T9831 20243-20246 NN denotes Apc
T9832 20247-20258 NNS denotes transcripts
T9833 20269-20277 VBN denotes analyzed
T9834 20259-20263 VBD denotes were
T9835 20264-20268 RB denotes also
T9836 20278-20280 IN denotes by
T9837 20281-20283 NN denotes RT
T9838 20284-20287 NN denotes PCR
T9839 20283-20284 HYPH denotes -
T9840 20288-20292 IN denotes with
T9841 20293-20300 NNS denotes primers
T9842 20301-20309 VBG denotes spanning
T9843 20310-20314 NN denotes exon
T9844 20315-20317 CD denotes 14
T9845 20318-20319 -LRB- denotes (
T9846 20326-20328 NN denotes 1A
T9847 20319-20325 NN denotes Figure
T9848 20328-20329 -RRB- denotes )
T9849 20330-20335 VBG denotes using
T9850 20336-20341 JJ denotes total
T9851 20342-20345 NN denotes RNA
T9852 20346-20354 VBN denotes isolated
T9853 20355-20359 IN denotes from
T9854 20360-20363 DT denotes the
T9855 20385-20392 NNS denotes samples
T9856 20364-20377 VBG denotes corresponding
T9857 20378-20384 NN denotes tissue
T9858 20392-20393 . denotes .
T9859 20393-20579 sentence denotes We detected the expected RT-PCR product (313 bp) from the truncated Apc (ApcΔ580) allele only in the tissues where Cre recombinase is known to be expressed in the K14-cre–positive mice.
T9860 20394-20396 PRP denotes We
T9861 20397-20405 VBD denotes detected
T9862 20406-20409 DT denotes the
T9863 20426-20433 NN denotes product
T9864 20410-20418 VBN denotes expected
T9865 20419-20421 NN denotes RT
T9866 20422-20425 NN denotes PCR
T9867 20421-20422 HYPH denotes -
T9868 20434-20435 -LRB- denotes (
T9869 20439-20441 NN denotes bp
T9870 20435-20438 CD denotes 313
T9871 20441-20442 -RRB- denotes )
T9872 20443-20447 IN denotes from
T9873 20448-20451 DT denotes the
T9874 20476-20482 NN denotes allele
T9875 20452-20461 VBN denotes truncated
T9876 20462-20465 NN denotes Apc
T9877 20466-20467 -LRB- denotes (
T9878 20467-20474 NN denotes ApcΔ580
T9879 20474-20475 -RRB- denotes )
T9880 20483-20487 RB denotes only
T9881 20488-20490 IN denotes in
T9882 20491-20494 DT denotes the
T9883 20495-20502 NNS denotes tissues
T9884 20503-20508 WRB denotes where
T9885 20528-20533 VBN denotes known
T9886 20509-20512 NN denotes Cre
T9887 20513-20524 NN denotes recombinase
T9888 20525-20527 VBZ denotes is
T9889 20534-20536 TO denotes to
T9890 20540-20549 VBN denotes expressed
T9891 20537-20539 VB denotes be
T9892 20550-20552 IN denotes in
T9893 20553-20556 DT denotes the
T9894 20574-20578 NNS denotes mice
T9895 20557-20560 NN denotes K14
T9896 20561-20564 NN denotes cre
T9897 20560-20561 HYPH denotes -
T9898 20565-20573 JJ denotes positive
T9899 20564-20565 HYPH denotes
T9900 20578-20579 . denotes .
T9901 20579-20927 sentence denotes However, this product was not detected in either the K14-cre–negative mouse tissues samples or the liver of K14-cre–positive mice, and only the product from the wild-type allele (528 bp) was detected from these RNA samples, further confirming that Cre-mediated recombination has taken place in the tissue- and genotype-specific manner (Figure 3B).
T9902 20580-20587 RB denotes However
T9903 20610-20618 VBN denotes detected
T9904 20587-20589 , denotes ,
T9905 20589-20593 DT denotes this
T9906 20594-20601 NN denotes product
T9907 20602-20605 VBD denotes was
T9908 20606-20609 RB denotes not
T9909 20619-20621 IN denotes in
T9910 20622-20628 CC denotes either
T9911 20664-20671 NNS denotes samples
T9912 20629-20632 DT denotes the
T9913 20633-20636 NN denotes K14
T9914 20637-20640 NN denotes cre
T9915 20636-20637 HYPH denotes -
T9916 20641-20649 JJ denotes negative
T9917 20640-20641 HYPH denotes
T9918 20650-20655 NN denotes mouse
T9919 20656-20663 NNS denotes tissues
T9920 20672-20674 CC denotes or
T9921 20675-20678 DT denotes the
T9922 20679-20684 NN denotes liver
T9923 20685-20687 IN denotes of
T9924 20688-20691 NN denotes K14
T9925 20692-20695 NN denotes cre
T9926 20691-20692 HYPH denotes -
T9927 20696-20704 JJ denotes positive
T9928 20695-20696 HYPH denotes
T9929 20705-20709 NNS denotes mice
T9930 20709-20711 , denotes ,
T9931 20711-20714 CC denotes and
T9932 20715-20719 RB denotes only
T9933 20724-20731 NN denotes product
T9934 20720-20723 DT denotes the
T9935 20771-20779 VBN denotes detected
T9936 20732-20736 IN denotes from
T9937 20737-20740 DT denotes the
T9938 20751-20757 NN denotes allele
T9939 20741-20745 JJ denotes wild
T9940 20746-20750 NN denotes type
T9941 20745-20746 HYPH denotes -
T9942 20758-20759 -LRB- denotes (
T9943 20763-20765 NN denotes bp
T9944 20759-20762 CD denotes 528
T9945 20765-20766 -RRB- denotes )
T9946 20767-20770 VBD denotes was
T9947 20780-20784 IN denotes from
T9948 20785-20790 DT denotes these
T9949 20795-20802 NNS denotes samples
T9950 20791-20794 NN denotes RNA
T9951 20802-20804 , denotes ,
T9952 20804-20811 RB denotes further
T9953 20812-20822 VBG denotes confirming
T9954 20823-20827 IN denotes that
T9955 20859-20864 VBN denotes taken
T9956 20828-20831 NN denotes Cre
T9957 20832-20840 JJ denotes mediated
T9958 20831-20832 HYPH denotes -
T9959 20841-20854 NN denotes recombination
T9960 20855-20858 VBZ denotes has
T9961 20865-20870 NN denotes place
T9962 20871-20873 IN denotes in
T9963 20874-20877 DT denotes the
T9964 20908-20914 NN denotes manner
T9965 20878-20884 NN denotes tissue
T9966 20899-20907 JJ denotes specific
T9967 20884-20885 HYPH denotes -
T9968 20886-20889 CC denotes and
T9969 20890-20898 NN denotes genotype
T9970 20898-20899 HYPH denotes -
T9971 20915-20916 -LRB- denotes (
T9972 20923-20925 NN denotes 3B
T9973 20916-20922 NN denotes Figure
T9974 20925-20926 -RRB- denotes )
T9975 20926-20927 . denotes .
T12568 20929-20932 JJ denotes K14
T12569 20933-20936 JJ denotes cre
T12570 20932-20933 HYPH denotes -
T12571 20937-20943 JJ denotes Driven
T12572 20936-20937 HYPH denotes
T12573 20975-20984 NNS denotes Follicles
T12574 20944-20947 NN denotes Apc
T12575 20948-20952 NN denotes Loss
T12576 20953-20960 VBN denotes Induced
T12577 20961-20969 NN denotes Aberrant
T12578 20970-20974 NN denotes Hair
T12579 20985-20995 IN denotes throughout
T12580 20996-20999 DT denotes the
T12581 21000-21009 NN denotes Epidermis
T12582 21009-21170 sentence denotes To understand the basis for delayed and abnormal hair development in the KA mutants, we conducted a histological and immunohistochemical examination (Figure 4).
T12583 21010-21012 TO denotes To
T12584 21013-21023 VB denotes understand
T12585 21098-21107 VBD denotes conducted
T12586 21024-21027 DT denotes the
T12587 21028-21033 NN denotes basis
T12588 21034-21037 IN denotes for
T12589 21038-21045 VBN denotes delayed
T12590 21064-21075 NN denotes development
T12591 21046-21049 CC denotes and
T12592 21050-21058 JJ denotes abnormal
T12593 21059-21063 NN denotes hair
T12594 21076-21078 IN denotes in
T12595 21079-21082 DT denotes the
T12596 21086-21093 NNS denotes mutants
T12597 21083-21085 NN denotes KA
T12598 21093-21095 , denotes ,
T12599 21095-21097 PRP denotes we
T12600 21108-21109 DT denotes a
T12601 21147-21158 NN denotes examination
T12602 21110-21122 JJ denotes histological
T12603 21123-21126 CC denotes and
T12604 21127-21146 JJ denotes immunohistochemical
T12605 21159-21160 -LRB- denotes (
T12606 21160-21166 NN denotes Figure
T12607 21167-21168 CD denotes 4
T12608 21168-21169 -RRB- denotes )
T12609 21169-21170 . denotes .
T12610 21170-21319 sentence denotes The hair follicle is an epidermal appendage that consists of an upper permanent portion, and a lower cycling portion that produces the hair [22,23].
T12611 21171-21174 DT denotes The
T12612 21180-21188 NN denotes follicle
T12613 21175-21179 NN denotes hair
T12614 21189-21191 VBZ denotes is
T12615 21192-21194 DT denotes an
T12616 21205-21214 NN denotes appendage
T12617 21195-21204 JJ denotes epidermal
T12618 21215-21219 WDT denotes that
T12619 21220-21228 VBZ denotes consists
T12620 21229-21231 IN denotes of
T12621 21232-21234 DT denotes an
T12622 21251-21258 NN denotes portion
T12623 21235-21240 JJ denotes upper
T12624 21241-21250 JJ denotes permanent
T12625 21258-21260 , denotes ,
T12626 21260-21263 CC denotes and
T12627 21264-21265 DT denotes a
T12628 21280-21287 NN denotes portion
T12629 21266-21271 JJR denotes lower
T12630 21272-21279 NN denotes cycling
T12631 21288-21292 WDT denotes that
T12632 21293-21301 VBZ denotes produces
T12633 21302-21305 DT denotes the
T12634 21306-21310 NN denotes hair
T12635 21311-21312 -LRB- denotes [
T12636 21315-21317 CD denotes 23
T12637 21312-21314 CD denotes 22
T12638 21314-21315 , denotes ,
T12639 21317-21318 -RRB- denotes ]
T12640 21318-21319 . denotes .
T12641 21319-21429 sentence denotes The outer root sheath (ORS) is contiguous with and biochemically similar to the basal layer of the epidermis.
T12642 21320-21323 DT denotes The
T12643 21335-21341 NN denotes sheath
T12644 21324-21329 JJ denotes outer
T12645 21330-21334 NN denotes root
T12646 21348-21350 VBZ denotes is
T12647 21342-21343 -LRB- denotes (
T12648 21343-21346 NN denotes ORS
T12649 21346-21347 -RRB- denotes )
T12650 21351-21361 JJ denotes contiguous
T12651 21362-21366 IN denotes with
T12652 21367-21370 CC denotes and
T12653 21371-21384 RB denotes biochemically
T12654 21385-21392 JJ denotes similar
T12655 21393-21395 IN denotes to
T12656 21396-21399 DT denotes the
T12657 21406-21411 NN denotes layer
T12658 21400-21405 JJ denotes basal
T12659 21412-21414 IN denotes of
T12660 21415-21418 DT denotes the
T12661 21419-21428 NN denotes epidermis
T12662 21428-21429 . denotes .
T12663 21429-21573 sentence denotes The inner layers of the hair follicle include three concentric layers of inner root sheath and three concentric layers of hair-producing cells.
T12664 21430-21433 DT denotes The
T12665 21440-21446 NNS denotes layers
T12666 21434-21439 JJ denotes inner
T12667 21468-21475 VBP denotes include
T12668 21447-21449 IN denotes of
T12669 21450-21453 DT denotes the
T12670 21459-21467 NN denotes follicle
T12671 21454-21458 NN denotes hair
T12672 21476-21481 CD denotes three
T12673 21493-21499 NNS denotes layers
T12674 21482-21492 JJ denotes concentric
T12675 21500-21502 IN denotes of
T12676 21503-21508 JJ denotes inner
T12677 21514-21520 NN denotes sheath
T12678 21509-21513 NN denotes root
T12679 21521-21524 CC denotes and
T12680 21525-21530 CD denotes three
T12681 21542-21548 NNS denotes layers
T12682 21531-21541 JJ denotes concentric
T12683 21549-21551 IN denotes of
T12684 21552-21556 NN denotes hair
T12685 21557-21566 VBG denotes producing
T12686 21556-21557 HYPH denotes -
T12687 21567-21572 NNS denotes cells
T12688 21572-21573 . denotes .
T12689 21573-21803 sentence denotes At the base of the hair follicle is the germinative hair follicle bulb, which contains rapidly proliferating “matrix” cells that differentiate to populate all of the layers of the inner root sheath and the hair shaft itself [22].
T12690 21574-21576 IN denotes At
T12691 21607-21609 VBZ denotes is
T12692 21577-21580 DT denotes the
T12693 21581-21585 NN denotes base
T12694 21586-21588 IN denotes of
T12695 21589-21592 DT denotes the
T12696 21598-21606 NN denotes follicle
T12697 21593-21597 NN denotes hair
T12698 21610-21613 DT denotes the
T12699 21640-21644 NN denotes bulb
T12700 21614-21625 JJ denotes germinative
T12701 21626-21630 NN denotes hair
T12702 21631-21639 NN denotes follicle
T12703 21644-21646 , denotes ,
T12704 21646-21651 WDT denotes which
T12705 21652-21660 VBZ denotes contains
T12706 21661-21668 RB denotes rapidly
T12707 21669-21682 VBG denotes proliferating
T12708 21692-21697 NNS denotes cells
T12709 21683-21684 `` denotes
T12710 21684-21690 NN denotes matrix
T12711 21690-21691 '' denotes
T12712 21698-21702 WDT denotes that
T12713 21703-21716 VBP denotes differentiate
T12714 21717-21719 TO denotes to
T12715 21720-21728 VB denotes populate
T12716 21729-21732 DT denotes all
T12717 21733-21735 IN denotes of
T12718 21736-21739 DT denotes the
T12719 21740-21746 NNS denotes layers
T12720 21747-21749 IN denotes of
T12721 21750-21753 DT denotes the
T12722 21765-21771 NN denotes sheath
T12723 21754-21759 JJ denotes inner
T12724 21760-21764 NN denotes root
T12725 21772-21775 CC denotes and
T12726 21776-21779 DT denotes the
T12727 21785-21790 NN denotes shaft
T12728 21780-21784 NN denotes hair
T12729 21791-21797 PRP denotes itself
T12730 21798-21799 -LRB- denotes [
T12731 21799-21801 CD denotes 22
T12732 21801-21802 -RRB- denotes ]
T12733 21802-21803 . denotes .
T12734 21803-22060 sentence denotes During the anagen phase of the hair cycle (until P15), hair follicles of phenotypically normal mice grew deeply into the subcutaneous fat and were uniformly spaced and aligned in parallel arrays at a specific angle relative to the skin surface (Figure 4A).
T12735 21804-21810 IN denotes During
T12736 21904-21908 VBD denotes grew
T12737 21811-21814 DT denotes the
T12738 21822-21827 NN denotes phase
T12739 21815-21821 NN denotes anagen
T12740 21828-21830 IN denotes of
T12741 21831-21834 DT denotes the
T12742 21840-21845 NN denotes cycle
T12743 21835-21839 NN denotes hair
T12744 21846-21847 -LRB- denotes (
T12745 21847-21852 IN denotes until
T12746 21853-21856 NN denotes P15
T12747 21856-21857 -RRB- denotes )
T12748 21857-21859 , denotes ,
T12749 21859-21863 NN denotes hair
T12750 21864-21873 NNS denotes follicles
T12751 21874-21876 IN denotes of
T12752 21877-21891 RB denotes phenotypically
T12753 21899-21903 NNS denotes mice
T12754 21892-21898 JJ denotes normal
T12755 21909-21915 RB denotes deeply
T12756 21916-21920 IN denotes into
T12757 21921-21924 DT denotes the
T12758 21938-21941 NN denotes fat
T12759 21925-21937 JJ denotes subcutaneous
T12760 21942-21945 CC denotes and
T12761 21946-21950 VBD denotes were
T12762 21961-21967 VBN denotes spaced
T12763 21951-21960 RB denotes uniformly
T12764 21968-21971 CC denotes and
T12765 21972-21979 VBN denotes aligned
T12766 21980-21982 IN denotes in
T12767 21983-21991 JJ denotes parallel
T12768 21992-21998 NNS denotes arrays
T12769 21999-22001 IN denotes at
T12770 22002-22003 DT denotes a
T12771 22013-22018 NN denotes angle
T12772 22004-22012 JJ denotes specific
T12773 22019-22027 JJ denotes relative
T12774 22028-22030 IN denotes to
T12775 22031-22034 DT denotes the
T12776 22040-22047 NN denotes surface
T12777 22035-22039 NN denotes skin
T12778 22048-22049 -LRB- denotes (
T12779 22056-22058 NN denotes 4A
T12780 22049-22055 NN denotes Figure
T12781 22058-22059 -RRB- denotes )
T12782 22059-22060 . denotes .
T12783 22060-22278 sentence denotes In contrast, KA mutant follicles were irregularly spaced and often seen as disoriented and clamped invaginations at P3 that became even more remarkable at P12 when the mutant mice were covered by fur coat (Figure 4F).
T12784 22061-22063 IN denotes In
T12785 22111-22117 VBN denotes spaced
T12786 22064-22072 NN denotes contrast
T12787 22072-22074 , denotes ,
T12788 22074-22076 NN denotes KA
T12789 22084-22093 NNS denotes follicles
T12790 22077-22083 JJ denotes mutant
T12791 22094-22098 VBD denotes were
T12792 22099-22110 RB denotes irregularly
T12793 22118-22121 CC denotes and
T12794 22122-22127 RB denotes often
T12795 22128-22132 VBN denotes seen
T12796 22133-22135 IN denotes as
T12797 22136-22147 JJ denotes disoriented
T12798 22160-22173 NNS denotes invaginations
T12799 22148-22151 CC denotes and
T12800 22152-22159 JJ denotes clamped
T12801 22174-22176 IN denotes at
T12802 22177-22179 NN denotes P3
T12803 22180-22184 WDT denotes that
T12804 22185-22191 VBD denotes became
T12805 22192-22196 RB denotes even
T12806 22197-22201 RBR denotes more
T12807 22202-22212 JJ denotes remarkable
T12808 22213-22215 IN denotes at
T12809 22216-22219 NN denotes P12
T12810 22220-22224 WRB denotes when
T12811 22246-22253 VBN denotes covered
T12812 22225-22228 DT denotes the
T12813 22236-22240 NNS denotes mice
T12814 22229-22235 JJ denotes mutant
T12815 22241-22245 VBD denotes were
T12816 22254-22256 IN denotes by
T12817 22257-22260 NN denotes fur
T12818 22261-22265 NN denotes coat
T12819 22266-22267 -LRB- denotes (
T12820 22274-22276 NN denotes 4F
T12821 22267-22273 NN denotes Figure
T12822 22276-22277 -RRB- denotes )
T12823 22277-22278 . denotes .
T12824 22278-22406 sentence denotes Bulbs were often bent in addition to being irregularly angled to one another and their sizes and locations were often variable.
T12825 22279-22284 NNS denotes Bulbs
T12826 22285-22289 VBD denotes were
T12827 22290-22295 RB denotes often
T12828 22296-22300 JJ denotes bent
T12829 22301-22303 IN denotes in
T12830 22304-22312 NN denotes addition
T12831 22313-22315 IN denotes to
T12832 22316-22321 VBG denotes being
T12833 22322-22333 RB denotes irregularly
T12834 22334-22340 JJ denotes angled
T12835 22341-22343 IN denotes to
T12836 22344-22347 NN denotes one
T12837 22348-22355 NN denotes another
T12838 22356-22359 CC denotes and
T12839 22360-22365 PRP$ denotes their
T12840 22366-22371 NNS denotes sizes
T12841 22386-22390 VBD denotes were
T12842 22372-22375 CC denotes and
T12843 22376-22385 NNS denotes locations
T12844 22391-22396 RB denotes often
T12845 22397-22405 JJ denotes variable
T12846 22405-22406 . denotes .
T12847 22406-22581 sentence denotes Clusters of multiple invaginations or dysplastic follicular structures were frequently observed throughout the epidermis, whereas other regions showed gaps with no follicles.
T12848 22407-22415 NNS denotes Clusters
T12849 22494-22502 VBN denotes observed
T12850 22416-22418 IN denotes of
T12851 22419-22427 JJ denotes multiple
T12852 22428-22441 NNS denotes invaginations
T12853 22442-22444 CC denotes or
T12854 22445-22455 JJ denotes dysplastic
T12855 22467-22477 NNS denotes structures
T12856 22456-22466 JJ denotes follicular
T12857 22478-22482 VBD denotes were
T12858 22483-22493 RB denotes frequently
T12859 22503-22513 IN denotes throughout
T12860 22514-22517 DT denotes the
T12861 22518-22527 NN denotes epidermis
T12862 22527-22529 , denotes ,
T12863 22529-22536 IN denotes whereas
T12864 22551-22557 VBD denotes showed
T12865 22537-22542 JJ denotes other
T12866 22543-22550 NNS denotes regions
T12867 22558-22562 NNS denotes gaps
T12868 22563-22567 IN denotes with
T12869 22568-22570 DT denotes no
T12870 22571-22580 NNS denotes follicles
T12871 22580-22581 . denotes .
T12872 22581-22713 sentence denotes Serial sectioning indicated that some of the hair follicles in the P12 mutant skin were not properly formed or shorter than normal.
T12873 22582-22588 JJ denotes Serial
T12874 22589-22599 NN denotes sectioning
T12875 22600-22609 VBD denotes indicated
T12876 22610-22614 IN denotes that
T12877 22665-22669 VBD denotes were
T12878 22615-22619 DT denotes some
T12879 22620-22622 IN denotes of
T12880 22623-22626 DT denotes the
T12881 22632-22641 NNS denotes follicles
T12882 22627-22631 NN denotes hair
T12883 22642-22644 IN denotes in
T12884 22645-22648 DT denotes the
T12885 22660-22664 NN denotes skin
T12886 22649-22652 NN denotes P12
T12887 22653-22659 JJ denotes mutant
T12888 22670-22673 RB denotes not
T12889 22674-22682 RB denotes properly
T12890 22683-22689 JJ denotes formed
T12891 22690-22692 CC denotes or
T12892 22693-22700 JJR denotes shorter
T12893 22701-22705 IN denotes than
T12894 22706-22712 JJ denotes normal
T12895 22712-22713 . denotes .
T12896 22713-22872 sentence denotes Taken together, these features could account for the apparently delayed, followed by outgrowth, of the short and shaggy-looking fur coat of these mutant mice.
T12897 22714-22719 VBN denotes Taken
T12898 22751-22758 VB denotes account
T12899 22720-22728 RB denotes together
T12900 22728-22730 , denotes ,
T12901 22730-22735 DT denotes these
T12902 22736-22744 NNS denotes features
T12903 22745-22750 MD denotes could
T12904 22759-22762 IN denotes for
T12905 22763-22766 DT denotes the
T12906 22778-22785 VBN denotes delayed
T12907 22767-22777 RB denotes apparently
T12908 22785-22787 , denotes ,
T12909 22787-22795 VBN denotes followed
T12910 22796-22798 IN denotes by
T12911 22799-22808 NN denotes outgrowth
T12912 22808-22810 , denotes ,
T12913 22810-22812 IN denotes of
T12914 22813-22816 DT denotes the
T12915 22846-22850 NN denotes coat
T12916 22817-22822 JJ denotes short
T12917 22823-22826 CC denotes and
T12918 22827-22833 JJ denotes shaggy
T12919 22834-22841 JJ denotes looking
T12920 22833-22834 HYPH denotes -
T12921 22842-22845 NN denotes fur
T12922 22851-22853 IN denotes of
T12923 22854-22859 DT denotes these
T12924 22867-22871 NNS denotes mice
T12925 22860-22866 JJ denotes mutant
T12926 22871-22872 . denotes .
T12927 22872-23845 sentence denotes Figure 4 Histological and Immunochemical Examination of P12 Skin and Teeth (A–E) P12 normal skin. (F–J) P12 mutant skin. (K–N) P12 normal oral cavity. (O–R) P12 mutant oral cavity. Stained with H&E for histology (A, F, K–L, O–P), Ki67 (B, G), β-catenin (C, H, M, Q), K14 (D, I, N, R), and K6 (E, J). Aberrant follicular morphogenesis, characterized by formation of irregularly spaced, nonpolarized hair follicles, in mutant skin is evident. Despite the abnormal histology, proliferation seems to be confined to hair bulb-like structures (arrows in [G], inset [G′] at higher magnification), but in mutant skin (arrows in [H], inset [H′] at higher magnification) and oral cavity (arrows in insets [Q′] at higher magnification) elevated cytosolic localization of β-catenin is detected in some cells. Scale bars: 50 μm for (A–F), (H–J); 250 μm for (K) and (O); 100 μm for (G), (L–N), (P–R); 20 μm for (Q′). Apc is a regulator of β-catenin that is important for Wnt signaling.
T12928 23777-23780 NN denotes Apc
T12929 23781-23783 VBZ denotes is
T12930 23784-23785 DT denotes a
T12931 23786-23795 NN denotes regulator
T12932 23796-23798 IN denotes of
T12933 23799-23800 NN denotes β
T12934 23801-23808 NN denotes catenin
T12935 23800-23801 HYPH denotes -
T12936 23809-23813 WDT denotes that
T12937 23814-23816 VBZ denotes is
T12938 23817-23826 JJ denotes important
T12939 23827-23830 IN denotes for
T12940 23831-23834 NN denotes Wnt
T12941 23835-23844 NN denotes signaling
T12942 23844-23845 . denotes .
T12943 23845-23922 sentence denotes We examined the patterns of expression of β-catenin in the affected tissues.
T12944 23846-23848 PRP denotes We
T12945 23849-23857 VBD denotes examined
T12946 23858-23861 DT denotes the
T12947 23862-23870 NNS denotes patterns
T12948 23871-23873 IN denotes of
T12949 23874-23884 NN denotes expression
T12950 23885-23887 IN denotes of
T12951 23888-23889 NN denotes β
T12952 23890-23897 NN denotes catenin
T12953 23889-23890 HYPH denotes -
T12954 23898-23900 IN denotes in
T12955 23901-23904 DT denotes the
T12956 23914-23921 NNS denotes tissues
T12957 23905-23913 JJ denotes affected
T12958 23921-23922 . denotes .
T12959 23922-24297 sentence denotes In the normal skin, β-catenin, a member of the adherens junction complex, was found in the ORS of hair follicles and basal layer of epidermis, where K14 expression is also observed (Figure 4C and 4D), whereas the expression of K1, involucrin, and loricrin (markers for spinous and granular layers of epidermis) was only observed in the nonbasal epidermis (unpublished data).
T12960 23923-23925 IN denotes In
T12961 24001-24006 VBN denotes found
T12962 23926-23929 DT denotes the
T12963 23937-23941 NN denotes skin
T12964 23930-23936 JJ denotes normal
T12965 23941-23943 , denotes ,
T12966 23943-23944 NN denotes β
T12967 23945-23952 NN denotes catenin
T12968 23944-23945 HYPH denotes -
T12969 23952-23954 , denotes ,
T12970 23954-23955 DT denotes a
T12971 23956-23962 NN denotes member
T12972 23963-23965 IN denotes of
T12973 23966-23969 DT denotes the
T12974 23988-23995 NN denotes complex
T12975 23970-23978 NNS denotes adherens
T12976 23979-23987 NN denotes junction
T12977 23995-23997 , denotes ,
T12978 23997-24000 VBD denotes was
T12979 24007-24009 IN denotes in
T12980 24010-24013 DT denotes the
T12981 24014-24017 NN denotes ORS
T12982 24018-24020 IN denotes of
T12983 24021-24025 NN denotes hair
T12984 24026-24035 NNS denotes follicles
T12985 24036-24039 CC denotes and
T12986 24040-24045 JJ denotes basal
T12987 24046-24051 NN denotes layer
T12988 24052-24054 IN denotes of
T12989 24055-24064 NN denotes epidermis
T12990 24064-24066 , denotes ,
T12991 24066-24071 WRB denotes where
T12992 24095-24103 VBN denotes observed
T12993 24072-24075 NN denotes K14
T12994 24076-24086 NN denotes expression
T12995 24087-24089 VBZ denotes is
T12996 24090-24094 RB denotes also
T12997 24104-24105 -LRB- denotes (
T12998 24112-24114 NN denotes 4C
T12999 24105-24111 NN denotes Figure
T13000 24115-24118 CC denotes and
T13001 24119-24121 NN denotes 4D
T13002 24121-24122 -RRB- denotes )
T13003 24122-24124 , denotes ,
T13004 24124-24131 IN denotes whereas
T13005 24243-24251 VBN denotes observed
T13006 24132-24135 DT denotes the
T13007 24136-24146 NN denotes expression
T13008 24147-24149 IN denotes of
T13009 24150-24152 NN denotes K1
T13010 24152-24154 , denotes ,
T13011 24154-24164 NN denotes involucrin
T13012 24164-24166 , denotes ,
T13013 24166-24169 CC denotes and
T13014 24170-24178 NN denotes loricrin
T13015 24179-24180 -LRB- denotes (
T13016 24180-24187 NNS denotes markers
T13017 24188-24191 IN denotes for
T13018 24192-24199 JJ denotes spinous
T13019 24213-24219 NNS denotes layers
T13020 24200-24203 CC denotes and
T13021 24204-24212 JJ denotes granular
T13022 24220-24222 IN denotes of
T13023 24223-24232 NN denotes epidermis
T13024 24232-24233 -RRB- denotes )
T13025 24234-24237 VBD denotes was
T13026 24238-24242 RB denotes only
T13027 24252-24254 IN denotes in
T13028 24255-24258 DT denotes the
T13029 24268-24277 NN denotes epidermis
T13030 24259-24267 JJ denotes nonbasal
T13031 24278-24279 -LRB- denotes (
T13032 24291-24295 NNS denotes data
T13033 24279-24290 JJ denotes unpublished
T13034 24295-24296 -RRB- denotes )
T13035 24296-24297 . denotes .
T13036 24297-24509 sentence denotes The patterns of expression of K14, K1, involucrin, and loricrin, in skin from mutant and normal littermate mice at P3–P17, showed no significant differences in the terminal differentiation (Figure 4A–4D, 4F–4I).
T13037 24298-24301 DT denotes The
T13038 24302-24310 NNS denotes patterns
T13039 24421-24427 VBD denotes showed
T13040 24311-24313 IN denotes of
T13041 24314-24324 NN denotes expression
T13042 24325-24327 IN denotes of
T13043 24328-24331 NN denotes K14
T13044 24331-24333 , denotes ,
T13045 24333-24335 NN denotes K1
T13046 24335-24337 , denotes ,
T13047 24337-24347 NN denotes involucrin
T13048 24347-24349 , denotes ,
T13049 24349-24352 CC denotes and
T13050 24353-24361 NN denotes loricrin
T13051 24361-24363 , denotes ,
T13052 24363-24365 IN denotes in
T13053 24366-24370 NN denotes skin
T13054 24371-24375 IN denotes from
T13055 24376-24382 JJ denotes mutant
T13056 24394-24404 JJ denotes littermate
T13057 24383-24386 CC denotes and
T13058 24387-24393 JJ denotes normal
T13059 24405-24409 NNS denotes mice
T13060 24410-24412 IN denotes at
T13061 24413-24415 NN denotes P3
T13062 24415-24416 SYM denotes
T13063 24416-24419 NN denotes P17
T13064 24419-24421 , denotes ,
T13065 24428-24430 DT denotes no
T13066 24443-24454 NNS denotes differences
T13067 24431-24442 JJ denotes significant
T13068 24455-24457 IN denotes in
T13069 24458-24461 DT denotes the
T13070 24471-24486 NN denotes differentiation
T13071 24462-24470 JJ denotes terminal
T13072 24487-24488 -LRB- denotes (
T13073 24495-24497 NN denotes 4A
T13074 24488-24494 NN denotes Figure
T13075 24497-24498 SYM denotes
T13076 24498-24500 NN denotes 4D
T13077 24500-24502 , denotes ,
T13078 24502-24504 NN denotes 4F
T13079 24504-24505 SYM denotes
T13080 24505-24507 NN denotes 4I
T13081 24507-24508 -RRB- denotes )
T13082 24508-24509 . denotes .
T13083 24509-24705 sentence denotes Similarly, the pattern of expression of K6, which is normally only expressed in the suprabasal or inner layer of the ORS of the hair follicle but not in the epidermis (Figure 4E), did not change.
T13084 24510-24519 RB denotes Similarly
T13085 24698-24704 VB denotes change
T13086 24519-24521 , denotes ,
T13087 24521-24524 DT denotes the
T13088 24525-24532 NN denotes pattern
T13089 24533-24535 IN denotes of
T13090 24536-24546 NN denotes expression
T13091 24547-24549 IN denotes of
T13092 24550-24552 NN denotes K6
T13093 24552-24554 , denotes ,
T13094 24554-24559 WDT denotes which
T13095 24577-24586 VBN denotes expressed
T13096 24560-24562 VBZ denotes is
T13097 24563-24571 RB denotes normally
T13098 24572-24576 RB denotes only
T13099 24587-24589 IN denotes in
T13100 24590-24593 DT denotes the
T13101 24614-24619 NN denotes layer
T13102 24594-24604 JJ denotes suprabasal
T13103 24605-24607 CC denotes or
T13104 24608-24613 JJ denotes inner
T13105 24620-24622 IN denotes of
T13106 24623-24626 DT denotes the
T13107 24627-24630 NN denotes ORS
T13108 24631-24633 IN denotes of
T13109 24634-24637 DT denotes the
T13110 24643-24651 NN denotes follicle
T13111 24638-24642 NN denotes hair
T13112 24652-24655 CC denotes but
T13113 24656-24659 RB denotes not
T13114 24660-24662 IN denotes in
T13115 24663-24666 DT denotes the
T13116 24667-24676 NN denotes epidermis
T13117 24677-24678 -LRB- denotes (
T13118 24685-24687 NN denotes 4E
T13119 24678-24684 NN denotes Figure
T13120 24687-24688 -RRB- denotes )
T13121 24688-24690 , denotes ,
T13122 24690-24693 VBD denotes did
T13123 24694-24697 RB denotes not
T13124 24704-24705 . denotes .
T13125 24705-24852 sentence denotes Due to the abnormal and disorganized structure of hair follicles themselves, K6 localization highlighted the histological abnormality (Figure 4J).
T13126 24706-24709 IN denotes Due
T13127 24799-24810 VBD denotes highlighted
T13128 24710-24712 IN denotes to
T13129 24713-24716 DT denotes the
T13130 24743-24752 NN denotes structure
T13131 24717-24725 JJ denotes abnormal
T13132 24726-24729 CC denotes and
T13133 24730-24742 JJ denotes disorganized
T13134 24753-24755 IN denotes of
T13135 24756-24760 NN denotes hair
T13136 24761-24770 NNS denotes follicles
T13137 24771-24781 PRP denotes themselves
T13138 24781-24783 , denotes ,
T13139 24783-24785 NN denotes K6
T13140 24786-24798 NN denotes localization
T13141 24811-24814 DT denotes the
T13142 24828-24839 NN denotes abnormality
T13143 24815-24827 JJ denotes histological
T13144 24840-24841 -LRB- denotes (
T13145 24848-24850 NN denotes 4J
T13146 24841-24847 NN denotes Figure
T13147 24850-24851 -RRB- denotes )
T13148 24851-24852 . denotes .
T13149 24852-25021 sentence denotes Yet as in the normal skin, K6 was principally seen only in the suprabasal layer of the ORS that did not colocalize with the basal markers, K14 or K5 (Figure 4I and 4J).
T13150 24853-24856 RB denotes Yet
T13151 24899-24903 VBN denotes seen
T13152 24857-24859 IN denotes as
T13153 24860-24862 IN denotes in
T13154 24863-24866 DT denotes the
T13155 24874-24878 NN denotes skin
T13156 24867-24873 JJ denotes normal
T13157 24878-24880 , denotes ,
T13158 24880-24882 NN denotes K6
T13159 24883-24886 VBD denotes was
T13160 24887-24898 RB denotes principally
T13161 24904-24908 RB denotes only
T13162 24909-24911 IN denotes in
T13163 24912-24915 DT denotes the
T13164 24927-24932 NN denotes layer
T13165 24916-24926 JJ denotes suprabasal
T13166 24933-24935 IN denotes of
T13167 24936-24939 DT denotes the
T13168 24940-24943 NN denotes ORS
T13169 24944-24948 WDT denotes that
T13170 24957-24967 VB denotes colocalize
T13171 24949-24952 VBD denotes did
T13172 24953-24956 RB denotes not
T13173 24968-24972 IN denotes with
T13174 24973-24976 DT denotes the
T13175 24983-24990 NNS denotes markers
T13176 24977-24982 JJ denotes basal
T13177 24990-24992 , denotes ,
T13178 24992-24995 NN denotes K14
T13179 24996-24998 CC denotes or
T13180 24999-25001 NN denotes K5
T13181 25002-25003 -LRB- denotes (
T13182 25010-25012 NN denotes 4I
T13183 25003-25009 NN denotes Figure
T13184 25013-25016 CC denotes and
T13185 25017-25019 NN denotes 4J
T13186 25019-25020 -RRB- denotes )
T13187 25020-25021 . denotes .
T13188 25021-25173 sentence denotes In normal skin, proliferating cells were detected in either the basal layer of epidermis or in germinative hair follicle bulbs at the base (Figure 4B).
T13189 25022-25024 IN denotes In
T13190 25063-25071 VBN denotes detected
T13191 25025-25031 JJ denotes normal
T13192 25032-25036 NN denotes skin
T13193 25036-25038 , denotes ,
T13194 25038-25051 VBG denotes proliferating
T13195 25052-25057 NNS denotes cells
T13196 25058-25062 VBD denotes were
T13197 25072-25074 IN denotes in
T13198 25075-25081 CC denotes either
T13199 25082-25085 DT denotes the
T13200 25092-25097 NN denotes layer
T13201 25086-25091 JJ denotes basal
T13202 25098-25100 IN denotes of
T13203 25101-25110 NN denotes epidermis
T13204 25111-25113 CC denotes or
T13205 25114-25116 IN denotes in
T13206 25117-25128 JJ denotes germinative
T13207 25143-25148 NNS denotes bulbs
T13208 25129-25133 NN denotes hair
T13209 25134-25142 NN denotes follicle
T13210 25149-25151 IN denotes at
T13211 25152-25155 DT denotes the
T13212 25156-25160 NN denotes base
T13213 25161-25162 -LRB- denotes (
T13214 25169-25171 NN denotes 4B
T13215 25162-25168 NN denotes Figure
T13216 25171-25172 -RRB- denotes )
T13217 25172-25173 . denotes .
T13218 25173-25431 sentence denotes In the mutant skin, either BrdU incorporation or Ki67 expression was observed not only in cells in bulbs at the base of the hair follicle but also in bulb-like structures that were budding out from the ORS of the existing hair follicles (Figure 4G and 4G′).
T13219 25174-25176 IN denotes In
T13220 25243-25251 VBN denotes observed
T13221 25177-25180 DT denotes the
T13222 25188-25192 NN denotes skin
T13223 25181-25187 JJ denotes mutant
T13224 25192-25194 , denotes ,
T13225 25194-25200 CC denotes either
T13226 25206-25219 NN denotes incorporation
T13227 25201-25205 NN denotes BrdU
T13228 25220-25222 CC denotes or
T13229 25223-25227 NN denotes Ki67
T13230 25228-25238 NN denotes expression
T13231 25239-25242 VBD denotes was
T13232 25252-25255 RB denotes not
T13233 25261-25263 IN denotes in
T13234 25256-25260 RB denotes only
T13235 25264-25269 NNS denotes cells
T13236 25270-25272 IN denotes in
T13237 25273-25278 NNS denotes bulbs
T13238 25279-25281 IN denotes at
T13239 25282-25285 DT denotes the
T13240 25286-25290 NN denotes base
T13241 25291-25293 IN denotes of
T13242 25294-25297 DT denotes the
T13243 25303-25311 NN denotes follicle
T13244 25298-25302 NN denotes hair
T13245 25312-25315 CC denotes but
T13246 25316-25320 RB denotes also
T13247 25321-25323 IN denotes in
T13248 25324-25328 NN denotes bulb
T13249 25329-25333 JJ denotes like
T13250 25328-25329 HYPH denotes -
T13251 25334-25344 NNS denotes structures
T13252 25345-25349 WDT denotes that
T13253 25355-25362 VBG denotes budding
T13254 25350-25354 VBD denotes were
T13255 25363-25366 RP denotes out
T13256 25367-25371 IN denotes from
T13257 25372-25375 DT denotes the
T13258 25376-25379 NN denotes ORS
T13259 25380-25382 IN denotes of
T13260 25383-25386 DT denotes the
T13261 25401-25410 NNS denotes follicles
T13262 25387-25395 VBG denotes existing
T13263 25396-25400 NN denotes hair
T13264 25411-25412 -LRB- denotes (
T13265 25419-25421 NN denotes 4G
T13266 25412-25418 NN denotes Figure
T13267 25422-25425 CC denotes and
T13268 25426-25428 NN denotes 4G
T13269 25428-25429 SYM denotes
T13270 25429-25430 -RRB- denotes )
T13271 25430-25431 . denotes .
T13272 25431-25519 sentence denotes Each budding tip was becoming like a hair follicle bulb containing proliferating cells.
T13273 25432-25436 DT denotes Each
T13274 25445-25448 NN denotes tip
T13275 25437-25444 VBG denotes budding
T13276 25453-25461 VBG denotes becoming
T13277 25449-25452 VBD denotes was
T13278 25462-25466 IN denotes like
T13279 25467-25468 DT denotes a
T13280 25483-25487 NN denotes bulb
T13281 25469-25473 NN denotes hair
T13282 25474-25482 NN denotes follicle
T13283 25488-25498 VBG denotes containing
T13284 25499-25512 VBG denotes proliferating
T13285 25513-25518 NNS denotes cells
T13286 25518-25519 . denotes .
T13287 25519-25679 sentence denotes Hence, despite the abnormal histology in the mutant skin, proliferation seems to be confined to bulb-like structures as in the normal skin (Figure 4G and 4G′).
T13288 25520-25525 RB denotes Hence
T13289 25592-25597 VBZ denotes seems
T13290 25525-25527 , denotes ,
T13291 25527-25534 IN denotes despite
T13292 25535-25538 DT denotes the
T13293 25548-25557 NN denotes histology
T13294 25539-25547 JJ denotes abnormal
T13295 25558-25560 IN denotes in
T13296 25561-25564 DT denotes the
T13297 25572-25576 NN denotes skin
T13298 25565-25571 JJ denotes mutant
T13299 25576-25578 , denotes ,
T13300 25578-25591 NN denotes proliferation
T13301 25598-25600 TO denotes to
T13302 25604-25612 VBN denotes confined
T13303 25601-25603 VB denotes be
T13304 25613-25615 IN denotes to
T13305 25616-25620 NN denotes bulb
T13306 25621-25625 JJ denotes like
T13307 25620-25621 HYPH denotes -
T13308 25626-25636 NNS denotes structures
T13309 25637-25639 IN denotes as
T13310 25640-25642 IN denotes in
T13311 25643-25646 DT denotes the
T13312 25654-25658 NN denotes skin
T13313 25647-25653 JJ denotes normal
T13314 25659-25660 -LRB- denotes (
T13315 25667-25669 NN denotes 4G
T13316 25660-25666 NN denotes Figure
T13317 25670-25673 CC denotes and
T13318 25674-25676 NN denotes 4G
T13319 25676-25677 SYM denotes
T13320 25677-25678 -RRB- denotes )
T13321 25678-25679 . denotes .
T13322 25679-25813 sentence denotes The exact locations of hair follicle bulbs were not as easy to define for some mutant follicles due to their disorganized structures.
T13323 25680-25683 DT denotes The
T13324 25690-25699 NNS denotes locations
T13325 25684-25689 JJ denotes exact
T13326 25723-25727 VBD denotes were
T13327 25700-25702 IN denotes of
T13328 25703-25707 NN denotes hair
T13329 25708-25716 NN denotes follicle
T13330 25717-25722 NNS denotes bulbs
T13331 25728-25731 RB denotes not
T13332 25732-25734 RB denotes as
T13333 25735-25739 JJ denotes easy
T13334 25740-25742 TO denotes to
T13335 25743-25749 VB denotes define
T13336 25750-25753 IN denotes for
T13337 25754-25758 DT denotes some
T13338 25766-25775 NNS denotes follicles
T13339 25759-25765 JJ denotes mutant
T13340 25776-25779 IN denotes due
T13341 25780-25782 IN denotes to
T13342 25783-25788 PRP$ denotes their
T13343 25802-25812 NNS denotes structures
T13344 25789-25801 JJ denotes disorganized
T13345 25812-25813 . denotes .
T13346 25813-26024 sentence denotes Interestingly, in the mutant skin, in addition to diffuse membrane-bound localization as in the normal skin, cells with strong cytosolic β-catenin localization were also observed frequently (Figure 4H and 4H′).
T13347 25814-25827 RB denotes Interestingly
T13348 25984-25992 VBN denotes observed
T13349 25827-25829 , denotes ,
T13350 25829-25831 IN denotes in
T13351 25832-25835 DT denotes the
T13352 25843-25847 NN denotes skin
T13353 25836-25842 JJ denotes mutant
T13354 25847-25849 , denotes ,
T13355 25849-25851 IN denotes in
T13356 25852-25860 NN denotes addition
T13357 25861-25863 IN denotes to
T13358 25864-25871 JJ denotes diffuse
T13359 25887-25899 NN denotes localization
T13360 25872-25880 NN denotes membrane
T13361 25881-25886 JJ denotes bound
T13362 25880-25881 HYPH denotes -
T13363 25900-25902 IN denotes as
T13364 25903-25905 IN denotes in
T13365 25906-25909 DT denotes the
T13366 25917-25921 NN denotes skin
T13367 25910-25916 JJ denotes normal
T13368 25921-25923 , denotes ,
T13369 25923-25928 NNS denotes cells
T13370 25929-25933 IN denotes with
T13371 25934-25940 JJ denotes strong
T13372 25961-25973 NN denotes localization
T13373 25941-25950 JJ denotes cytosolic
T13374 25951-25952 NN denotes β
T13375 25952-25953 HYPH denotes -
T13376 25953-25960 NN denotes catenin
T13377 25974-25978 VBD denotes were
T13378 25979-25983 RB denotes also
T13379 25993-26003 RB denotes frequently
T13380 26004-26005 -LRB- denotes (
T13381 26012-26014 NN denotes 4H
T13382 26005-26011 NN denotes Figure
T13383 26015-26018 CC denotes and
T13384 26019-26021 NN denotes 4H
T13385 26021-26022 SYM denotes
T13386 26022-26023 -RRB- denotes )
T13387 26023-26024 . denotes .
T13388 26024-26144 sentence denotes These elevated β-catenin–expressing cells were usually surrounded by proliferating cells, forming bulb-like structures.
T13389 26025-26030 DT denotes These
T13390 26061-26066 NNS denotes cells
T13391 26031-26039 JJ denotes elevated
T13392 26040-26041 NN denotes β
T13393 26042-26049 NN denotes catenin
T13394 26041-26042 HYPH denotes -
T13395 26050-26060 VBG denotes expressing
T13396 26049-26050 HYPH denotes
T13397 26080-26090 VBN denotes surrounded
T13398 26067-26071 VBD denotes were
T13399 26072-26079 RB denotes usually
T13400 26091-26093 IN denotes by
T13401 26094-26107 VBG denotes proliferating
T13402 26108-26113 NNS denotes cells
T13403 26113-26115 , denotes ,
T13404 26115-26122 VBG denotes forming
T13405 26123-26127 NN denotes bulb
T13406 26128-26132 JJ denotes like
T13407 26127-26128 HYPH denotes -
T13408 26133-26143 NNS denotes structures
T13409 26143-26144 . denotes .
T13410 26144-26413 sentence denotes Comparison of immunochemically stained serial sections showed that these intense cytosolic β-catenin stainings were usually found in either K14-positive K1-negative basal epidermis or K14-positive K6-negative basal ORS cells, and are surrounded by proliferating cells.
T13411 26145-26155 NN denotes Comparison
T13412 26200-26206 VBD denotes showed
T13413 26156-26158 IN denotes of
T13414 26159-26175 RB denotes immunochemically
T13415 26176-26183 VBN denotes stained
T13416 26191-26199 NNS denotes sections
T13417 26184-26190 JJ denotes serial
T13418 26207-26211 IN denotes that
T13419 26269-26274 VBN denotes found
T13420 26212-26217 DT denotes these
T13421 26246-26255 NNS denotes stainings
T13422 26218-26225 JJ denotes intense
T13423 26226-26235 JJ denotes cytosolic
T13424 26236-26237 NN denotes β
T13425 26237-26238 HYPH denotes -
T13426 26238-26245 NN denotes catenin
T13427 26256-26260 VBD denotes were
T13428 26261-26268 RB denotes usually
T13429 26275-26277 IN denotes in
T13430 26278-26284 CC denotes either
T13431 26316-26325 NN denotes epidermis
T13432 26285-26288 NN denotes K14
T13433 26289-26297 JJ denotes positive
T13434 26288-26289 HYPH denotes -
T13435 26298-26300 NN denotes K1
T13436 26301-26309 JJ denotes negative
T13437 26300-26301 HYPH denotes -
T13438 26310-26315 JJ denotes basal
T13439 26326-26328 CC denotes or
T13440 26329-26332 NN denotes K14
T13441 26333-26341 JJ denotes positive
T13442 26332-26333 HYPH denotes -
T13443 26364-26369 NNS denotes cells
T13444 26342-26344 NN denotes K6
T13445 26345-26353 JJ denotes negative
T13446 26344-26345 HYPH denotes -
T13447 26354-26359 JJ denotes basal
T13448 26360-26363 NN denotes ORS
T13449 26369-26371 , denotes ,
T13450 26371-26374 CC denotes and
T13451 26375-26378 VBP denotes are
T13452 26379-26389 VBN denotes surrounded
T13453 26390-26392 IN denotes by
T13454 26393-26406 VBG denotes proliferating
T13455 26407-26412 NNS denotes cells
T13456 26412-26413 . denotes .
T13457 26413-26613 sentence denotes To determine the initiation of hair follicle morphogenesis in these mutants, we examined the expression pattern of Sonic hedgehog (Shh), a factor expressed in hair bulbs in embryonic skin (Figure 5).
T13458 26414-26416 TO denotes To
T13459 26417-26426 VB denotes determine
T13460 26494-26502 VBD denotes examined
T13461 26427-26430 DT denotes the
T13462 26431-26441 NN denotes initiation
T13463 26442-26444 IN denotes of
T13464 26445-26449 NN denotes hair
T13465 26450-26458 NN denotes follicle
T13466 26459-26472 NN denotes morphogenesis
T13467 26473-26475 IN denotes in
T13468 26476-26481 DT denotes these
T13469 26482-26489 NNS denotes mutants
T13470 26489-26491 , denotes ,
T13471 26491-26493 PRP denotes we
T13472 26503-26506 DT denotes the
T13473 26518-26525 NN denotes pattern
T13474 26507-26517 NN denotes expression
T13475 26526-26528 IN denotes of
T13476 26529-26534 NNP denotes Sonic
T13477 26535-26543 NNP denotes hedgehog
T13478 26544-26545 -LRB- denotes (
T13479 26545-26548 NN denotes Shh
T13480 26548-26549 -RRB- denotes )
T13481 26549-26551 , denotes ,
T13482 26551-26552 DT denotes a
T13483 26553-26559 NN denotes factor
T13484 26560-26569 VBN denotes expressed
T13485 26570-26572 IN denotes in
T13486 26573-26577 NN denotes hair
T13487 26578-26583 NNS denotes bulbs
T13488 26584-26586 IN denotes in
T13489 26587-26596 JJ denotes embryonic
T13490 26597-26601 NN denotes skin
T13491 26602-26603 -LRB- denotes (
T13492 26603-26609 NN denotes Figure
T13493 26610-26611 CD denotes 5
T13494 26611-26612 -RRB- denotes )
T13495 26612-26613 . denotes .
T13496 26613-26873 sentence denotes The aberrant hair follicle morphogenesis is evident as early as E14.5 in mutant embryonic skin, by multiple apolarized expression of Shh throughout the epidermis (Figure 5B), whereas that of control embryos was well polarized and regularly spaced (Figure 5A).
T13497 26614-26617 DT denotes The
T13498 26641-26654 NN denotes morphogenesis
T13499 26618-26626 JJ denotes aberrant
T13500 26627-26631 NN denotes hair
T13501 26632-26640 NN denotes follicle
T13502 26655-26657 VBZ denotes is
T13503 26658-26665 JJ denotes evident
T13504 26666-26668 RB denotes as
T13505 26669-26674 RB denotes early
T13506 26675-26677 IN denotes as
T13507 26678-26683 NN denotes E14.5
T13508 26684-26686 IN denotes in
T13509 26687-26693 JJ denotes mutant
T13510 26704-26708 NN denotes skin
T13511 26694-26703 JJ denotes embryonic
T13512 26708-26710 , denotes ,
T13513 26710-26712 IN denotes by
T13514 26713-26721 JJ denotes multiple
T13515 26733-26743 NN denotes expression
T13516 26722-26732 JJ denotes apolarized
T13517 26744-26746 IN denotes of
T13518 26747-26750 NN denotes Shh
T13519 26751-26761 IN denotes throughout
T13520 26762-26765 DT denotes the
T13521 26766-26775 NN denotes epidermis
T13522 26776-26777 -LRB- denotes (
T13523 26784-26786 NN denotes 5B
T13524 26777-26783 NN denotes Figure
T13525 26786-26787 -RRB- denotes )
T13526 26787-26789 , denotes ,
T13527 26789-26796 IN denotes whereas
T13528 26821-26824 VBD denotes was
T13529 26797-26801 DT denotes that
T13530 26802-26804 IN denotes of
T13531 26805-26812 NN denotes control
T13532 26813-26820 NNS denotes embryos
T13533 26825-26829 RB denotes well
T13534 26830-26839 JJ denotes polarized
T13535 26840-26843 CC denotes and
T13536 26844-26853 RB denotes regularly
T13537 26854-26860 JJ denotes spaced
T13538 26861-26862 -LRB- denotes (
T13539 26869-26871 NN denotes 5A
T13540 26862-26868 NN denotes Figure
T13541 26871-26872 -RRB- denotes )
T13542 26872-26873 . denotes .
T13543 26873-27061 sentence denotes With development, control mouse hair follicles invaginate downward in a polarized manner (Figure 5C), whereas those of mutant embryos were completely irregular and apolarized (Figure 5D).
T13544 26874-26878 IN denotes With
T13545 26921-26931 VBP denotes invaginate
T13546 26879-26890 NN denotes development
T13547 26890-26892 , denotes ,
T13548 26892-26899 NN denotes control
T13549 26900-26905 NN denotes mouse
T13550 26911-26920 NNS denotes follicles
T13551 26906-26910 NN denotes hair
T13552 26932-26940 RB denotes downward
T13553 26941-26943 IN denotes in
T13554 26944-26945 DT denotes a
T13555 26956-26962 NN denotes manner
T13556 26946-26955 VBN denotes polarized
T13557 26963-26964 -LRB- denotes (
T13558 26971-26973 NN denotes 5C
T13559 26964-26970 NN denotes Figure
T13560 26973-26974 -RRB- denotes )
T13561 26974-26976 , denotes ,
T13562 26976-26983 IN denotes whereas
T13563 27008-27012 VBD denotes were
T13564 26984-26989 DT denotes those
T13565 26990-26992 IN denotes of
T13566 26993-26999 JJ denotes mutant
T13567 27000-27007 NNS denotes embryos
T13568 27013-27023 RB denotes completely
T13569 27024-27033 JJ denotes irregular
T13570 27034-27037 CC denotes and
T13571 27038-27048 JJ denotes apolarized
T13572 27049-27050 -LRB- denotes (
T13573 27057-27059 NN denotes 5D
T13574 27050-27056 NN denotes Figure
T13575 27059-27060 -RRB- denotes )
T13576 27060-27061 . denotes .
T13577 27061-27178 sentence denotes It was also noted that the size of each “budding” follicle, as detected by Shh expression, was variable (Figure 5D).
T13578 27062-27064 PRP denotes It
T13579 27074-27079 VBN denotes noted
T13580 27065-27068 VBD denotes was
T13581 27069-27073 RB denotes also
T13582 27080-27084 IN denotes that
T13583 27153-27156 VBD denotes was
T13584 27085-27088 DT denotes the
T13585 27089-27093 NN denotes size
T13586 27094-27096 IN denotes of
T13587 27097-27101 DT denotes each
T13588 27112-27120 NN denotes follicle
T13589 27102-27103 `` denotes
T13590 27103-27110 NN denotes budding
T13591 27110-27111 '' denotes
T13592 27120-27122 , denotes ,
T13593 27122-27124 IN denotes as
T13594 27125-27133 VBN denotes detected
T13595 27134-27136 IN denotes by
T13596 27137-27140 NN denotes Shh
T13597 27141-27151 NN denotes expression
T13598 27151-27153 , denotes ,
T13599 27157-27165 JJ denotes variable
T13600 27166-27167 -LRB- denotes (
T13601 27174-27176 NN denotes 5D
T13602 27167-27173 NN denotes Figure
T13603 27176-27177 -RRB- denotes )
T13604 27177-27178 . denotes .
T13605 27178-27271 sentence denotes The intensity of Shh staining was generally stronger in mutant skin than in the normal skin.
T13606 27179-27182 DT denotes The
T13607 27183-27192 NN denotes intensity
T13608 27209-27212 VBD denotes was
T13609 27193-27195 IN denotes of
T13610 27196-27199 NN denotes Shh
T13611 27200-27208 NN denotes staining
T13612 27213-27222 RB denotes generally
T13613 27223-27231 JJR denotes stronger
T13614 27232-27234 IN denotes in
T13615 27235-27241 JJ denotes mutant
T13616 27242-27246 NN denotes skin
T13617 27247-27251 IN denotes than
T13618 27252-27254 IN denotes in
T13619 27255-27258 DT denotes the
T13620 27266-27270 NN denotes skin
T13621 27259-27265 JJ denotes normal
T13622 27270-27271 . denotes .
T13623 27271-27485 sentence denotes The aberrant initiation of multiple hair placodes during early hair follicle morphogenesis was also evident by the whole-mount in situ hybridization (ISH) of E15.5 mutant embryos for β-catenin (Figure 5F and 5F′).
T13624 27272-27275 DT denotes The
T13625 27285-27295 NN denotes initiation
T13626 27276-27284 JJ denotes aberrant
T13627 27363-27366 VBD denotes was
T13628 27296-27298 IN denotes of
T13629 27299-27307 JJ denotes multiple
T13630 27313-27321 NNS denotes placodes
T13631 27308-27312 NN denotes hair
T13632 27322-27328 IN denotes during
T13633 27329-27334 JJ denotes early
T13634 27349-27362 NN denotes morphogenesis
T13635 27335-27339 NN denotes hair
T13636 27340-27348 NN denotes follicle
T13637 27367-27371 RB denotes also
T13638 27372-27379 JJ denotes evident
T13639 27380-27382 IN denotes by
T13640 27383-27386 DT denotes the
T13641 27393-27398 NN denotes mount
T13642 27387-27392 JJ denotes whole
T13643 27392-27393 HYPH denotes -
T13644 27399-27401 FW denotes in
T13645 27402-27406 FW denotes situ
T13646 27407-27420 NN denotes hybridization
T13647 27421-27422 -LRB- denotes (
T13648 27422-27425 NN denotes ISH
T13649 27425-27426 -RRB- denotes )
T13650 27427-27429 IN denotes of
T13651 27430-27435 NN denotes E15.5
T13652 27443-27450 NNS denotes embryos
T13653 27436-27442 JJ denotes mutant
T13654 27451-27454 IN denotes for
T13655 27455-27456 NN denotes β
T13656 27457-27464 NN denotes catenin
T13657 27456-27457 HYPH denotes -
T13658 27465-27466 -LRB- denotes (
T13659 27473-27475 NN denotes 5F
T13660 27466-27472 NN denotes Figure
T13661 27476-27479 CC denotes and
T13662 27480-27482 NN denotes 5F
T13663 27482-27483 SYM denotes
T13664 27483-27484 -RRB- denotes )
T13665 27484-27485 . denotes .
T13666 27485-27795 sentence denotes The expression pattern of β-catenin in embryos clearly demonstrated the formation of regular arrays of hair placodes in the normal embryonic skin (Figure 5E and 5E′), but such regular patterning was lost, and often tightly clustered abnormal hair placodes were initiated in mutant embryonic skin (Figure 5F′).
T13667 27486-27489 DT denotes The
T13668 27501-27508 NN denotes pattern
T13669 27490-27500 NN denotes expression
T13670 27541-27553 VBD denotes demonstrated
T13671 27509-27511 IN denotes of
T13672 27512-27513 NN denotes β
T13673 27514-27521 NN denotes catenin
T13674 27513-27514 HYPH denotes -
T13675 27522-27524 IN denotes in
T13676 27525-27532 NNS denotes embryos
T13677 27533-27540 RB denotes clearly
T13678 27554-27557 DT denotes the
T13679 27558-27567 NN denotes formation
T13680 27568-27570 IN denotes of
T13681 27571-27578 JJ denotes regular
T13682 27579-27585 NNS denotes arrays
T13683 27586-27588 IN denotes of
T13684 27589-27593 NN denotes hair
T13685 27594-27602 NNS denotes placodes
T13686 27603-27605 IN denotes in
T13687 27606-27609 DT denotes the
T13688 27627-27631 NN denotes skin
T13689 27610-27616 JJ denotes normal
T13690 27617-27626 JJ denotes embryonic
T13691 27632-27633 -LRB- denotes (
T13692 27640-27642 NN denotes 5E
T13693 27633-27639 NN denotes Figure
T13694 27643-27646 CC denotes and
T13695 27647-27649 NN denotes 5E
T13696 27649-27650 SYM denotes
T13697 27650-27651 -RRB- denotes )
T13698 27651-27653 , denotes ,
T13699 27653-27656 CC denotes but
T13700 27657-27661 JJ denotes such
T13701 27670-27680 NN denotes patterning
T13702 27662-27669 JJ denotes regular
T13703 27685-27689 VBN denotes lost
T13704 27681-27684 VBD denotes was
T13705 27689-27691 , denotes ,
T13706 27691-27694 CC denotes and
T13707 27695-27700 RB denotes often
T13708 27747-27756 VBN denotes initiated
T13709 27701-27708 RB denotes tightly
T13710 27709-27718 VBN denotes clustered
T13711 27733-27741 NNS denotes placodes
T13712 27719-27727 JJ denotes abnormal
T13713 27728-27732 NN denotes hair
T13714 27742-27746 VBD denotes were
T13715 27757-27759 IN denotes in
T13716 27760-27766 JJ denotes mutant
T13717 27767-27776 JJ denotes embryonic
T13718 27777-27781 NN denotes skin
T13719 27782-27783 -LRB- denotes (
T13720 27790-27792 NN denotes 5F
T13721 27783-27789 NN denotes Figure
T13722 27792-27793 SYM denotes
T13723 27793-27794 -RRB- denotes )
T13724 27794-27795 . denotes .
T13725 27795-27972 sentence denotes Aberrant hair placodes were also evident throughout the skin surface of limbs in E15.5 mutants (Figure 5F), whereas those of the control embryos had not yet formed (Figure 5E).
T13726 27796-27804 JJ denotes Aberrant
T13727 27810-27818 NNS denotes placodes
T13728 27805-27809 NN denotes hair
T13729 27819-27823 VBD denotes were
T13730 27824-27828 RB denotes also
T13731 27829-27836 JJ denotes evident
T13732 27837-27847 IN denotes throughout
T13733 27848-27851 DT denotes the
T13734 27857-27864 NN denotes surface
T13735 27852-27856 NN denotes skin
T13736 27865-27867 IN denotes of
T13737 27868-27873 NNS denotes limbs
T13738 27874-27876 IN denotes in
T13739 27877-27882 NN denotes E15.5
T13740 27883-27890 NNS denotes mutants
T13741 27891-27892 -LRB- denotes (
T13742 27899-27901 NN denotes 5F
T13743 27892-27898 NN denotes Figure
T13744 27901-27902 -RRB- denotes )
T13745 27902-27904 , denotes ,
T13746 27904-27911 IN denotes whereas
T13747 27953-27959 VBN denotes formed
T13748 27912-27917 DT denotes those
T13749 27918-27920 IN denotes of
T13750 27921-27924 DT denotes the
T13751 27933-27940 NNS denotes embryos
T13752 27925-27932 NN denotes control
T13753 27941-27944 VBD denotes had
T13754 27945-27948 RB denotes not
T13755 27949-27952 RB denotes yet
T13756 27960-27961 -LRB- denotes (
T13757 27968-27970 NN denotes 5E
T13758 27961-27967 NN denotes Figure
T13759 27970-27971 -RRB- denotes )
T13760 27971-27972 . denotes .
T13761 27972-28256 sentence denotes Most interestingly, in the mutant footpads, where hair placodes do not normally form (Figure 5G), we also found ectopic irregularly sized and spaced hair placodes, indicating that the footpads still have the potential to form hair placodes in the absence of the Apc gene (Figure 5H).
T13762 27973-27977 RBS denotes Most
T13763 27978-27991 RB denotes interestingly
T13764 28079-28084 VBD denotes found
T13765 27991-27993 , denotes ,
T13766 27993-27995 IN denotes in
T13767 27996-27999 DT denotes the
T13768 28007-28015 NNS denotes footpads
T13769 28000-28006 JJ denotes mutant
T13770 28015-28017 , denotes ,
T13771 28017-28022 WRB denotes where
T13772 28053-28057 VB denotes form
T13773 28023-28027 NN denotes hair
T13774 28028-28036 NNS denotes placodes
T13775 28037-28039 VBP denotes do
T13776 28040-28043 RB denotes not
T13777 28044-28052 RB denotes normally
T13778 28058-28059 -LRB- denotes (
T13779 28066-28068 NN denotes 5G
T13780 28059-28065 NN denotes Figure
T13781 28068-28069 -RRB- denotes )
T13782 28069-28071 , denotes ,
T13783 28071-28073 PRP denotes we
T13784 28074-28078 RB denotes also
T13785 28085-28092 JJ denotes ectopic
T13786 28127-28135 NNS denotes placodes
T13787 28093-28104 RB denotes irregularly
T13788 28105-28110 VBN denotes sized
T13789 28111-28114 CC denotes and
T13790 28115-28121 VBN denotes spaced
T13791 28122-28126 NN denotes hair
T13792 28135-28137 , denotes ,
T13793 28137-28147 VBG denotes indicating
T13794 28148-28152 IN denotes that
T13795 28172-28176 VBP denotes have
T13796 28153-28156 DT denotes the
T13797 28157-28165 NNS denotes footpads
T13798 28166-28171 RB denotes still
T13799 28177-28180 DT denotes the
T13800 28181-28190 NN denotes potential
T13801 28191-28193 TO denotes to
T13802 28194-28198 VB denotes form
T13803 28199-28203 NN denotes hair
T13804 28204-28212 NNS denotes placodes
T13805 28213-28215 IN denotes in
T13806 28216-28219 DT denotes the
T13807 28220-28227 NN denotes absence
T13808 28228-28230 IN denotes of
T13809 28231-28234 DT denotes the
T13810 28239-28243 NN denotes gene
T13811 28235-28238 NN denotes Apc
T13812 28244-28245 -LRB- denotes (
T13813 28252-28254 NN denotes 5H
T13814 28245-28251 NN denotes Figure
T13815 28254-28255 -RRB- denotes )
T13816 28255-28256 . denotes .
T13817 28256-29203 sentence denotes Figure 5 Expression of Shh and β-catenin Transcripts in Normal (ApcCKO/CKO) and Mutant (K14-cre; ApcCKO/CKO) Embryonic Skin (A–D) Section ISH with Shh probe in E14.5 normal (A), E14.5 mutant (B), E16.5 normal (C), and E16.5 mutant (D) skin. Broken lines indicate the interface between epithelium and mesenchyme. Scale bars: 50 μm. Whole mount in situ detection of β-catenin in E15.5 normal (E, G), mutant (F, H) embryos. Aberrant initiation of multiple hair placodes is evident at E14.5. Loss of K14-driven Apc loss caused aberrant pattern formation (F′) and formed ectopic hair placodes in normally hairless foot pads (H, arrows) which are absent in normal (G). These results collectively suggest that the terminal differentiation does take place normally in the mutant skin, but initiation of embryonic hair follicle morphogenesis is severely disrupted, accompanied by a continuous ectopic hair follicle morphogenesis in postnatal mutant skin.
T13818 28921-28926 DT denotes These
T13819 28927-28934 NNS denotes results
T13820 28948-28955 VBP denotes suggest
T13821 28935-28947 RB denotes collectively
T13822 28956-28960 IN denotes that
T13823 28995-28999 VB denotes take
T13824 28961-28964 DT denotes the
T13825 28974-28989 NN denotes differentiation
T13826 28965-28973 JJ denotes terminal
T13827 28990-28994 VBZ denotes does
T13828 29000-29005 NN denotes place
T13829 29006-29014 RB denotes normally
T13830 29015-29017 IN denotes in
T13831 29018-29021 DT denotes the
T13832 29029-29033 NN denotes skin
T13833 29022-29028 JJ denotes mutant
T13834 29033-29035 , denotes ,
T13835 29035-29038 CC denotes but
T13836 29039-29049 NN denotes initiation
T13837 29114-29125 VBN denotes accompanied
T13838 29050-29052 IN denotes of
T13839 29053-29062 JJ denotes embryonic
T13840 29077-29090 NN denotes morphogenesis
T13841 29063-29067 NN denotes hair
T13842 29068-29076 NN denotes follicle
T13843 29091-29093 VBZ denotes is
T13844 29094-29102 RB denotes severely
T13845 29103-29112 VBN denotes disrupted
T13846 29112-29114 , denotes ,
T13847 29126-29128 IN denotes by
T13848 29129-29130 DT denotes a
T13849 29164-29177 NN denotes morphogenesis
T13850 29131-29141 JJ denotes continuous
T13851 29142-29149 JJ denotes ectopic
T13852 29150-29154 NN denotes hair
T13853 29155-29163 NN denotes follicle
T13854 29178-29180 IN denotes in
T13855 29181-29190 JJ denotes postnatal
T13856 29198-29202 NN denotes skin
T13857 29191-29197 JJ denotes mutant
T13858 29202-29203 . denotes .
T14505 29205-29212 NNS denotes Effects
T14506 29213-29215 IN denotes of
T14507 29216-29219 NN denotes K14
T14508 29220-29223 NN denotes cre
T14509 29219-29220 HYPH denotes -
T14510 29224-29230 VBN denotes Driven
T14511 29223-29224 HYPH denotes
T14512 29231-29235 NN denotes Loss
T14513 29236-29238 IN denotes of
T14514 29239-29242 NN denotes Apc
T14515 29243-29245 IN denotes in
T14516 29246-29251 JJ denotes Other
T14517 29262-29272 NNS denotes Appendages
T14518 29252-29261 JJ denotes Epidermal
T14519 29272-29473 sentence denotes Similar to the biology of hair follicles, K14-cre–driven loss of Apc also affected the development of other epidermal appendages that depend on epithelial–mesenchymal interactions for their formation.
T14520 29273-29280 JJ denotes Similar
T14521 29347-29355 VBD denotes affected
T14522 29281-29283 IN denotes to
T14523 29284-29287 DT denotes the
T14524 29288-29295 NN denotes biology
T14525 29296-29298 IN denotes of
T14526 29299-29303 NN denotes hair
T14527 29304-29313 NNS denotes follicles
T14528 29313-29315 , denotes ,
T14529 29315-29318 NN denotes K14
T14530 29319-29322 NN denotes cre
T14531 29318-29319 HYPH denotes -
T14532 29323-29329 VBN denotes driven
T14533 29322-29323 HYPH denotes
T14534 29330-29334 NN denotes loss
T14535 29335-29337 IN denotes of
T14536 29338-29341 NN denotes Apc
T14537 29342-29346 RB denotes also
T14538 29356-29359 DT denotes the
T14539 29360-29371 NN denotes development
T14540 29372-29374 IN denotes of
T14541 29375-29380 JJ denotes other
T14542 29391-29401 NNS denotes appendages
T14543 29381-29390 JJ denotes epidermal
T14544 29402-29406 WDT denotes that
T14545 29407-29413 VBP denotes depend
T14546 29414-29416 IN denotes on
T14547 29417-29427 JJ denotes epithelial
T14548 29428-29439 JJ denotes mesenchymal
T14549 29427-29428 HYPH denotes
T14550 29440-29452 NNS denotes interactions
T14551 29453-29456 IN denotes for
T14552 29457-29462 PRP$ denotes their
T14553 29463-29472 NN denotes formation
T14554 29472-29473 . denotes .
T14555 29473-29537 sentence denotes The most striking of these was dental dysplasia (Figure 4K–4R).
T14556 29474-29477 DT denotes The
T14557 29483-29491 JJ denotes striking
T14558 29478-29482 RBS denotes most
T14559 29501-29504 VBD denotes was
T14560 29492-29494 IN denotes of
T14561 29495-29500 DT denotes these
T14562 29505-29511 JJ denotes dental
T14563 29512-29521 NN denotes dysplasia
T14564 29522-29523 -LRB- denotes (
T14565 29530-29532 NN denotes 4K
T14566 29523-29529 NN denotes Figure
T14567 29532-29533 SYM denotes
T14568 29533-29535 NN denotes 4R
T14569 29535-29536 -RRB- denotes )
T14570 29536-29537 . denotes .
T14571 29537-29739 sentence denotes Tooth development is normally initiated between E11 and E12 by invagination of ectodermally derived oral epithelium into the underlying cranial neural crest–derived mesenchyme, generating a tooth germ.
T14572 29538-29543 NN denotes Tooth
T14573 29544-29555 NN denotes development
T14574 29568-29577 VBN denotes initiated
T14575 29556-29558 VBZ denotes is
T14576 29559-29567 RB denotes normally
T14577 29578-29585 IN denotes between
T14578 29586-29589 NN denotes E11
T14579 29590-29593 CC denotes and
T14580 29594-29597 NN denotes E12
T14581 29598-29600 IN denotes by
T14582 29601-29613 NN denotes invagination
T14583 29614-29616 IN denotes of
T14584 29617-29629 RB denotes ectodermally
T14585 29630-29637 VBN denotes derived
T14586 29643-29653 NN denotes epithelium
T14587 29638-29642 JJ denotes oral
T14588 29654-29658 IN denotes into
T14589 29659-29662 DT denotes the
T14590 29703-29713 NN denotes mesenchyme
T14591 29663-29673 VBG denotes underlying
T14592 29674-29681 JJ denotes cranial
T14593 29689-29694 NN denotes crest
T14594 29682-29688 JJ denotes neural
T14595 29695-29702 VBN denotes derived
T14596 29694-29695 HYPH denotes
T14597 29713-29715 , denotes ,
T14598 29715-29725 VBG denotes generating
T14599 29726-29727 DT denotes a
T14600 29734-29738 NN denotes germ
T14601 29728-29733 JJ denotes tooth
T14602 29738-29739 . denotes .
T14603 29739-29903 sentence denotes Despite the grossly toothless phenotype of KA mutants, histological analysis of their oral cavities revealed the formation of multiple tooth buds at each location.
T14604 29740-29747 IN denotes Despite
T14605 29840-29848 VBD denotes revealed
T14606 29748-29751 DT denotes the
T14607 29770-29779 NN denotes phenotype
T14608 29752-29759 RB denotes grossly
T14609 29760-29769 JJ denotes toothless
T14610 29780-29782 IN denotes of
T14611 29783-29785 NN denotes KA
T14612 29786-29793 NNS denotes mutants
T14613 29793-29795 , denotes ,
T14614 29795-29807 JJ denotes histological
T14615 29808-29816 NN denotes analysis
T14616 29817-29819 IN denotes of
T14617 29820-29825 PRP$ denotes their
T14618 29831-29839 NNS denotes cavities
T14619 29826-29830 JJ denotes oral
T14620 29849-29852 DT denotes the
T14621 29853-29862 NN denotes formation
T14622 29863-29865 IN denotes of
T14623 29866-29874 JJ denotes multiple
T14624 29881-29885 NNS denotes buds
T14625 29875-29880 JJ denotes tooth
T14626 29886-29888 IN denotes at
T14627 29889-29893 DT denotes each
T14628 29894-29902 NN denotes location
T14629 29902-29903 . denotes .
T14630 29903-30008 sentence denotes These aberrant teeth obviously failed to grow out during the dietary transition from milk to solid food.
T14631 29904-29909 DT denotes These
T14632 29919-29924 NNS denotes teeth
T14633 29910-29918 JJ denotes aberrant
T14634 29935-29941 VBD denotes failed
T14635 29925-29934 RB denotes obviously
T14636 29942-29944 TO denotes to
T14637 29945-29949 VB denotes grow
T14638 29950-29953 RP denotes out
T14639 29954-29960 IN denotes during
T14640 29961-29964 DT denotes the
T14641 29973-29983 NN denotes transition
T14642 29965-29972 JJ denotes dietary
T14643 29984-29988 IN denotes from
T14644 29989-29993 NN denotes milk
T14645 29994-29996 IN denotes to
T14646 29997-30002 JJ denotes solid
T14647 30003-30007 NN denotes food
T14648 30007-30008 . denotes .
T14649 30008-30212 sentence denotes Analogous to the expression patterns of K14 and β-catenin in the normal skin, diffuse membrane-bound expression of β-catenin was detected in K14-expressing oral epithelium and ameloblasts of normal mice.
T14650 30009-30018 JJ denotes Analogous
T14651 30138-30146 VBN denotes detected
T14652 30019-30021 IN denotes to
T14653 30022-30025 DT denotes the
T14654 30037-30045 NNS denotes patterns
T14655 30026-30036 NN denotes expression
T14656 30046-30048 IN denotes of
T14657 30049-30052 NN denotes K14
T14658 30053-30056 CC denotes and
T14659 30057-30058 NN denotes β
T14660 30059-30066 NN denotes catenin
T14661 30058-30059 HYPH denotes -
T14662 30067-30069 IN denotes in
T14663 30070-30073 DT denotes the
T14664 30081-30085 NN denotes skin
T14665 30074-30080 JJ denotes normal
T14666 30085-30087 , denotes ,
T14667 30087-30094 JJ denotes diffuse
T14668 30110-30120 NN denotes expression
T14669 30095-30103 NN denotes membrane
T14670 30104-30109 VBN denotes bound
T14671 30103-30104 HYPH denotes -
T14672 30121-30123 IN denotes of
T14673 30124-30125 NN denotes β
T14674 30126-30133 NN denotes catenin
T14675 30125-30126 HYPH denotes -
T14676 30134-30137 VBD denotes was
T14677 30147-30149 IN denotes in
T14678 30150-30153 NN denotes K14
T14679 30154-30164 VBG denotes expressing
T14680 30153-30154 HYPH denotes -
T14681 30170-30180 NN denotes epithelium
T14682 30165-30169 JJ denotes oral
T14683 30181-30184 CC denotes and
T14684 30185-30196 NNS denotes ameloblasts
T14685 30197-30199 IN denotes of
T14686 30200-30206 JJ denotes normal
T14687 30207-30211 NNS denotes mice
T14688 30211-30212 . denotes .
T14689 30212-30371 sentence denotes In mutants, some of the K14-expressing cells also showed strong cytosolic/nuclear β-catenin staining, as observed in the mutant skin (Figure 4Q, 4Q′, and 4R).
T14690 30213-30215 IN denotes In
T14691 30263-30269 VBD denotes showed
T14692 30216-30223 NNS denotes mutants
T14693 30223-30225 , denotes ,
T14694 30225-30229 DT denotes some
T14695 30230-30232 IN denotes of
T14696 30233-30236 DT denotes the
T14697 30252-30257 NNS denotes cells
T14698 30237-30240 NN denotes K14
T14699 30241-30251 VBG denotes expressing
T14700 30240-30241 HYPH denotes -
T14701 30258-30262 RB denotes also
T14702 30270-30276 JJ denotes strong
T14703 30305-30313 NN denotes staining
T14704 30277-30286 JJ denotes cytosolic
T14705 30295-30296 NN denotes β
T14706 30286-30287 HYPH denotes /
T14707 30287-30294 JJ denotes nuclear
T14708 30296-30297 HYPH denotes -
T14709 30297-30304 NN denotes catenin
T14710 30313-30315 , denotes ,
T14711 30315-30317 IN denotes as
T14712 30318-30326 VBN denotes observed
T14713 30327-30329 IN denotes in
T14714 30330-30333 DT denotes the
T14715 30341-30345 NN denotes skin
T14716 30334-30340 JJ denotes mutant
T14717 30346-30347 -LRB- denotes (
T14718 30354-30356 NN denotes 4Q
T14719 30347-30353 NN denotes Figure
T14720 30356-30358 , denotes ,
T14721 30358-30360 NN denotes 4Q
T14722 30360-30361 SYM denotes
T14723 30361-30363 , denotes ,
T14724 30363-30366 CC denotes and
T14725 30367-30369 NN denotes 4R
T14726 30369-30370 -RRB- denotes )
T14727 30370-30371 . denotes .
T14728 30371-30524 sentence denotes Initiation of ectopic tooth buds in the mutant mice was evident at E15.5 by extra dots of Shh expression adjacent to the primary teeth (data not shown).
T14729 30372-30382 NN denotes Initiation
T14730 30424-30427 VBD denotes was
T14731 30383-30385 IN denotes of
T14732 30386-30393 JJ denotes ectopic
T14733 30400-30404 NNS denotes buds
T14734 30394-30399 JJ denotes tooth
T14735 30405-30407 IN denotes in
T14736 30408-30411 DT denotes the
T14737 30419-30423 NNS denotes mice
T14738 30412-30418 JJ denotes mutant
T14739 30428-30435 JJ denotes evident
T14740 30436-30438 IN denotes at
T14741 30439-30444 NN denotes E15.5
T14742 30445-30447 IN denotes by
T14743 30448-30453 JJ denotes extra
T14744 30454-30458 NNS denotes dots
T14745 30459-30461 IN denotes of
T14746 30462-30465 NN denotes Shh
T14747 30466-30476 NN denotes expression
T14748 30477-30485 JJ denotes adjacent
T14749 30486-30488 IN denotes to
T14750 30489-30492 DT denotes the
T14751 30501-30506 NNS denotes teeth
T14752 30493-30500 JJ denotes primary
T14753 30507-30508 -LRB- denotes (
T14754 30517-30522 VBN denotes shown
T14755 30508-30512 NNS denotes data
T14756 30513-30516 RB denotes not
T14757 30522-30523 -RRB- denotes )
T14758 30523-30524 . denotes .
T14759 30524-30652 sentence denotes Loss of Apc also leads to hyperplasia in squamous epithelia of cornea, oral, salivary, and Hardarian glands (unpublished data).
T14760 30525-30529 NN denotes Loss
T14761 30542-30547 VBZ denotes leads
T14762 30530-30532 IN denotes of
T14763 30533-30536 NN denotes Apc
T14764 30537-30541 RB denotes also
T14765 30548-30550 IN denotes to
T14766 30551-30562 NN denotes hyperplasia
T14767 30563-30565 IN denotes in
T14768 30566-30574 JJ denotes squamous
T14769 30575-30584 NNS denotes epithelia
T14770 30585-30587 IN denotes of
T14771 30588-30594 NN denotes cornea
T14772 30626-30632 NNS denotes glands
T14773 30594-30596 , denotes ,
T14774 30596-30600 JJ denotes oral
T14775 30600-30602 , denotes ,
T14776 30602-30610 JJ denotes salivary
T14777 30610-30612 , denotes ,
T14778 30612-30615 CC denotes and
T14779 30616-30625 JJ denotes Hardarian
T14780 30633-30634 -LRB- denotes (
T14781 30646-30650 NNS denotes data
T14782 30634-30645 JJ denotes unpublished
T14783 30650-30651 -RRB- denotes )
T14784 30651-30652 . denotes .
T14785 30652-30780 sentence denotes Squamous metaplasia to hair follicle–like structures, ectopic hair follicle morphogenesis was also observed in these epithelia.
T14786 30653-30661 JJ denotes Squamous
T14787 30662-30672 NN denotes metaplasia
T14788 30752-30760 VBN denotes observed
T14789 30673-30675 IN denotes to
T14790 30676-30680 NN denotes hair
T14791 30681-30689 NN denotes follicle
T14792 30690-30694 JJ denotes like
T14793 30689-30690 HYPH denotes
T14794 30695-30705 NNS denotes structures
T14795 30705-30707 , denotes ,
T14796 30707-30714 JJ denotes ectopic
T14797 30729-30742 NN denotes morphogenesis
T14798 30715-30719 NN denotes hair
T14799 30720-30728 NN denotes follicle
T14800 30743-30746 VBD denotes was
T14801 30747-30751 RB denotes also
T14802 30761-30763 IN denotes in
T14803 30764-30769 DT denotes these
T14804 30770-30779 NNS denotes epithelia
T14805 30779-30780 . denotes .
T17241 30782-30785 NN denotes K14
T17242 30786-30789 NN denotes cre
T17243 30785-30786 HYPH denotes -
T17244 30790-30796 VBN denotes Driven
T17245 30789-30790 HYPH denotes
T17246 30801-30805 NN denotes Loss
T17247 30797-30800 NN denotes Apc
T17248 30806-30813 VBZ denotes Results
T17249 30814-30816 IN denotes in
T17250 30817-30828 JJ denotes Hypoplastic
T17251 30829-30836 JJ denotes Athymic
T17252 30828-30829 HYPH denotes /
T17253 30837-30841 NNS denotes Mice
T17254 30841-30908 sentence denotes Thymus is an organ that is also known to have K14 expression [16].
T17255 30842-30848 NN denotes Thymus
T17256 30849-30851 VBZ denotes is
T17257 30852-30854 DT denotes an
T17258 30855-30860 NN denotes organ
T17259 30861-30865 WDT denotes that
T17260 30874-30879 VBN denotes known
T17261 30866-30868 VBZ denotes is
T17262 30869-30873 RB denotes also
T17263 30880-30882 TO denotes to
T17264 30883-30887 VB denotes have
T17265 30888-30891 NN denotes K14
T17266 30892-30902 NN denotes expression
T17267 30903-30904 -LRB- denotes [
T17268 30904-30906 CD denotes 16
T17269 30906-30907 -RRB- denotes ]
T17270 30907-30908 . denotes .
T17271 30908-30990 sentence denotes It represents the primary lymphoid organ for thymocyte development and selection.
T17272 30909-30911 PRP denotes It
T17273 30912-30922 VBZ denotes represents
T17274 30923-30926 DT denotes the
T17275 30944-30949 NN denotes organ
T17276 30927-30934 JJ denotes primary
T17277 30935-30943 JJ denotes lymphoid
T17278 30950-30953 IN denotes for
T17279 30954-30963 NN denotes thymocyte
T17280 30964-30975 NN denotes development
T17281 30976-30979 CC denotes and
T17282 30980-30989 NN denotes selection
T17283 30989-30990 . denotes .
T17284 30990-31083 sentence denotes Distinct population of TECs of cortex and medulla mediates both of these critical functions.
T17285 30991-30999 JJ denotes Distinct
T17286 31000-31010 NN denotes population
T17287 31041-31049 VBZ denotes mediates
T17288 31011-31013 IN denotes of
T17289 31014-31018 NNS denotes TECs
T17290 31019-31021 IN denotes of
T17291 31022-31028 NN denotes cortex
T17292 31029-31032 CC denotes and
T17293 31033-31040 NN denotes medulla
T17294 31050-31054 DT denotes both
T17295 31055-31057 IN denotes of
T17296 31058-31063 DT denotes these
T17297 31073-31082 NNS denotes functions
T17298 31064-31072 JJ denotes critical
T17299 31082-31083 . denotes .
T17300 31083-31210 sentence denotes Cortical and medullary TEC subsets are characterized by differential expression of four keratin species: K8, K18, K5, and K14.
T17301 31084-31092 JJ denotes Cortical
T17302 31111-31118 NNS denotes subsets
T17303 31093-31096 CC denotes and
T17304 31097-31106 JJ denotes medullary
T17305 31107-31110 NN denotes TEC
T17306 31123-31136 VBN denotes characterized
T17307 31119-31122 VBP denotes are
T17308 31137-31139 IN denotes by
T17309 31140-31152 JJ denotes differential
T17310 31153-31163 NN denotes expression
T17311 31164-31166 IN denotes of
T17312 31167-31171 CD denotes four
T17313 31180-31187 NNS denotes species
T17314 31172-31179 NN denotes keratin
T17315 31187-31189 : denotes :
T17316 31189-31191 NN denotes K8
T17317 31191-31193 , denotes ,
T17318 31193-31196 NN denotes K18
T17319 31196-31198 , denotes ,
T17320 31198-31200 NN denotes K5
T17321 31200-31202 , denotes ,
T17322 31202-31205 CC denotes and
T17323 31206-31209 NN denotes K14
T17324 31209-31210 . denotes .
T17325 31210-31371 sentence denotes The normal thymus is a lobulated lymphoid organ, each lobule clearly showing the two distinct TEC compartments, an outer cortex and an inner medulla (Figure 6).
T17326 31211-31214 DT denotes The
T17327 31222-31228 NN denotes thymus
T17328 31215-31221 JJ denotes normal
T17329 31229-31231 VBZ denotes is
T17330 31232-31233 DT denotes a
T17331 31253-31258 NN denotes organ
T17332 31234-31243 VBN denotes lobulated
T17333 31244-31252 JJ denotes lymphoid
T17334 31258-31260 , denotes ,
T17335 31260-31264 DT denotes each
T17336 31265-31271 NN denotes lobule
T17337 31280-31287 VBG denotes showing
T17338 31272-31279 RB denotes clearly
T17339 31288-31291 DT denotes the
T17340 31309-31321 NNS denotes compartments
T17341 31292-31295 CD denotes two
T17342 31296-31304 JJ denotes distinct
T17343 31305-31308 NN denotes TEC
T17344 31321-31323 , denotes ,
T17345 31323-31325 DT denotes an
T17346 31332-31338 NN denotes cortex
T17347 31326-31331 JJ denotes outer
T17348 31339-31342 CC denotes and
T17349 31343-31345 DT denotes an
T17350 31352-31359 NN denotes medulla
T17351 31346-31351 JJ denotes inner
T17352 31360-31361 -LRB- denotes (
T17353 31361-31367 NN denotes Figure
T17354 31368-31369 CD denotes 6
T17355 31369-31370 -RRB- denotes )
T17356 31370-31371 . denotes .
T17357 31371-31495 sentence denotes There were no major differences in the histology of thymus between the ages P3 to P17 in phenotypically normal littermates.
T17358 31372-31377 EX denotes There
T17359 31378-31382 VBD denotes were
T17360 31383-31385 DT denotes no
T17361 31392-31403 NNS denotes differences
T17362 31386-31391 JJ denotes major
T17363 31404-31406 IN denotes in
T17364 31407-31410 DT denotes the
T17365 31411-31420 NN denotes histology
T17366 31421-31423 IN denotes of
T17367 31424-31430 NN denotes thymus
T17368 31431-31438 IN denotes between
T17369 31439-31442 DT denotes the
T17370 31443-31447 NNS denotes ages
T17371 31448-31450 NN denotes P3
T17372 31451-31453 IN denotes to
T17373 31454-31457 NN denotes P17
T17374 31458-31460 IN denotes in
T17375 31461-31475 RB denotes phenotypically
T17376 31476-31482 JJ denotes normal
T17377 31483-31494 NNS denotes littermates
T17378 31494-31495 . denotes .
T17379 31495-31614 sentence denotes As shown in the H&E staining of thymus, the cortex was formed of dense lymphoid tissue that lacks nodules (Figure 6A).
T17380 31496-31498 IN denotes As
T17381 31499-31504 VBN denotes shown
T17382 31551-31557 VBN denotes formed
T17383 31505-31507 IN denotes in
T17384 31508-31511 DT denotes the
T17385 31516-31524 NN denotes staining
T17386 31512-31513 NN denotes H
T17387 31513-31514 CC denotes &
T17388 31514-31515 NN denotes E
T17389 31525-31527 IN denotes of
T17390 31528-31534 NN denotes thymus
T17391 31534-31536 , denotes ,
T17392 31536-31539 DT denotes the
T17393 31540-31546 NN denotes cortex
T17394 31547-31550 VBD denotes was
T17395 31558-31560 IN denotes of
T17396 31561-31566 JJ denotes dense
T17397 31576-31582 NN denotes tissue
T17398 31567-31575 JJ denotes lymphoid
T17399 31583-31587 WDT denotes that
T17400 31588-31593 VBZ denotes lacks
T17401 31594-31601 NNS denotes nodules
T17402 31602-31603 -LRB- denotes (
T17403 31610-31612 NN denotes 6A
T17404 31603-31609 NN denotes Figure
T17405 31612-31613 -RRB- denotes )
T17406 31613-31614 . denotes .
T17407 31614-31758 sentence denotes Since the stroma of the medulla is less heavily infiltrated with lymphocytes than the cortex, the medulla stained more lightly than the cortex.
T17408 31615-31620 IN denotes Since
T17409 31647-31649 VBZ denotes is
T17410 31621-31624 DT denotes the
T17411 31625-31631 NN denotes stroma
T17412 31632-31634 IN denotes of
T17413 31635-31638 DT denotes the
T17414 31639-31646 NN denotes medulla
T17415 31721-31728 VBD denotes stained
T17416 31650-31654 RBR denotes less
T17417 31655-31662 RB denotes heavily
T17418 31663-31674 JJ denotes infiltrated
T17419 31675-31679 IN denotes with
T17420 31680-31691 NNS denotes lymphocytes
T17421 31692-31696 IN denotes than
T17422 31697-31700 DT denotes the
T17423 31701-31707 NN denotes cortex
T17424 31707-31709 , denotes ,
T17425 31709-31712 DT denotes the
T17426 31713-31720 NN denotes medulla
T17427 31729-31733 RBR denotes more
T17428 31734-31741 RB denotes lightly
T17429 31742-31746 IN denotes than
T17430 31747-31750 DT denotes the
T17431 31751-31757 NN denotes cortex
T17432 31757-31758 . denotes .
T17433 31758-31865 sentence denotes In normal mice, the thymus retains its size until the young adult age and regresses thereafter by atrophy.
T17434 31759-31761 IN denotes In
T17435 31786-31793 VBZ denotes retains
T17436 31762-31768 JJ denotes normal
T17437 31769-31773 NNS denotes mice
T17438 31773-31775 , denotes ,
T17439 31775-31778 DT denotes the
T17440 31779-31785 NN denotes thymus
T17441 31794-31797 PRP$ denotes its
T17442 31798-31802 NN denotes size
T17443 31803-31808 IN denotes until
T17444 31809-31812 DT denotes the
T17445 31825-31828 NN denotes age
T17446 31813-31818 JJ denotes young
T17447 31819-31824 JJ denotes adult
T17448 31829-31832 CC denotes and
T17449 31833-31842 VBZ denotes regresses
T17450 31843-31853 RB denotes thereafter
T17451 31854-31856 IN denotes by
T17452 31857-31864 NN denotes atrophy
T17453 31864-31865 . denotes .
T17454 31865-32030 sentence denotes In the normal young mice we examined (P3–P17), it is evident that thymocytes were mitotically active in the cortex as determined by BrdU immunostaining (Figure 6B).
T17455 31866-31868 IN denotes In
T17456 31916-31918 VBZ denotes is
T17457 31869-31872 DT denotes the
T17458 31886-31890 NNS denotes mice
T17459 31873-31879 JJ denotes normal
T17460 31880-31885 JJ denotes young
T17461 31891-31893 PRP denotes we
T17462 31894-31902 VBD denotes examined
T17463 31903-31904 -LRB- denotes (
T17464 31904-31906 NN denotes P3
T17465 31906-31907 SYM denotes
T17466 31907-31910 NN denotes P17
T17467 31910-31911 -RRB- denotes )
T17468 31911-31913 , denotes ,
T17469 31913-31915 PRP denotes it
T17470 31919-31926 JJ denotes evident
T17471 31927-31931 IN denotes that
T17472 31943-31947 VBD denotes were
T17473 31932-31942 NNS denotes thymocytes
T17474 31948-31959 RB denotes mitotically
T17475 31960-31966 JJ denotes active
T17476 31967-31969 IN denotes in
T17477 31970-31973 DT denotes the
T17478 31974-31980 NN denotes cortex
T17479 31981-31983 IN denotes as
T17480 31984-31994 VBN denotes determined
T17481 31995-31997 IN denotes by
T17482 31998-32002 NN denotes BrdU
T17483 32003-32017 NN denotes immunostaining
T17484 32018-32019 -LRB- denotes (
T17485 32026-32028 NN denotes 6B
T17486 32019-32025 NN denotes Figure
T17487 32028-32029 -RRB- denotes )
T17488 32029-32030 . denotes .
T17489 32030-32290 sentence denotes Immunohistochemistry of normal thymus from P3 to P17 mice showed a similar staining pattern for K14 in that its expression was restricted to a small population of TECs in the inner medullary region and in the keratinocytes in Hassall's corpuscles (Figure 6D).
T17490 32031-32051 NN denotes Immunohistochemistry
T17491 32089-32095 VBD denotes showed
T17492 32052-32054 IN denotes of
T17493 32055-32061 JJ denotes normal
T17494 32062-32068 NN denotes thymus
T17495 32069-32073 IN denotes from
T17496 32074-32076 NN denotes P3
T17497 32084-32088 NNS denotes mice
T17498 32077-32079 IN denotes to
T17499 32080-32083 NN denotes P17
T17500 32096-32097 DT denotes a
T17501 32115-32122 NN denotes pattern
T17502 32098-32105 JJ denotes similar
T17503 32106-32114 NN denotes staining
T17504 32123-32126 IN denotes for
T17505 32127-32130 NN denotes K14
T17506 32131-32133 IN denotes in
T17507 32158-32168 VBN denotes restricted
T17508 32134-32138 IN denotes that
T17509 32139-32142 PRP$ denotes its
T17510 32143-32153 NN denotes expression
T17511 32154-32157 VBD denotes was
T17512 32169-32171 IN denotes to
T17513 32172-32173 DT denotes a
T17514 32180-32190 NN denotes population
T17515 32174-32179 JJ denotes small
T17516 32191-32193 IN denotes of
T17517 32194-32198 NNS denotes TECs
T17518 32199-32201 IN denotes in
T17519 32202-32205 DT denotes the
T17520 32222-32228 NN denotes region
T17521 32206-32211 JJ denotes inner
T17522 32212-32221 JJ denotes medullary
T17523 32229-32232 CC denotes and
T17524 32233-32235 IN denotes in
T17525 32236-32239 DT denotes the
T17526 32240-32253 NNS denotes keratinocytes
T17527 32254-32256 IN denotes in
T17528 32257-32264 NNP denotes Hassall
T17529 32267-32277 NNS denotes corpuscles
T17530 32264-32266 POS denotes 's
T17531 32278-32279 -LRB- denotes (
T17532 32286-32288 NN denotes 6D
T17533 32279-32285 NN denotes Figure
T17534 32288-32289 -RRB- denotes )
T17535 32289-32290 . denotes .
T17536 32290-32398 sentence denotes Diffuse cytoplasmic staining for β-catenin was also detected in the medullary epithelial cells (Figure 6C).
T17537 32291-32298 JJ denotes Diffuse
T17538 32311-32319 NN denotes staining
T17539 32299-32310 JJ denotes cytoplasmic
T17540 32343-32351 VBN denotes detected
T17541 32320-32323 IN denotes for
T17542 32324-32325 NN denotes β
T17543 32326-32333 NN denotes catenin
T17544 32325-32326 HYPH denotes -
T17545 32334-32337 VBD denotes was
T17546 32338-32342 RB denotes also
T17547 32352-32354 IN denotes in
T17548 32355-32358 DT denotes the
T17549 32380-32385 NNS denotes cells
T17550 32359-32368 JJ denotes medullary
T17551 32369-32379 JJ denotes epithelial
T17552 32386-32387 -LRB- denotes (
T17553 32394-32396 NN denotes 6C
T17554 32387-32393 NN denotes Figure
T17555 32396-32397 -RRB- denotes )
T17556 32397-32398 . denotes .
T17557 32398-32530 sentence denotes In contrast to K14 expression, diffuse staining for K8 was observed in epithelial cells both in the medulla and cortex (Figure S3).
T17558 32399-32401 IN denotes In
T17559 32458-32466 VBN denotes observed
T17560 32402-32410 NN denotes contrast
T17561 32411-32413 IN denotes to
T17562 32414-32417 NN denotes K14
T17563 32418-32428 NN denotes expression
T17564 32428-32430 , denotes ,
T17565 32430-32437 JJ denotes diffuse
T17566 32438-32446 NN denotes staining
T17567 32447-32450 IN denotes for
T17568 32451-32453 NN denotes K8
T17569 32454-32457 VBD denotes was
T17570 32467-32469 IN denotes in
T17571 32470-32480 JJ denotes epithelial
T17572 32481-32486 NNS denotes cells
T17573 32487-32491 CC denotes both
T17574 32492-32494 IN denotes in
T17575 32495-32498 DT denotes the
T17576 32499-32506 NN denotes medulla
T17577 32507-32510 CC denotes and
T17578 32511-32517 NN denotes cortex
T17579 32518-32519 -LRB- denotes (
T17580 32526-32528 NN denotes S3
T17581 32519-32525 NN denotes Figure
T17582 32528-32529 -RRB- denotes )
T17583 32529-32530 . denotes .
T17584 32530-32690 sentence denotes K1 staining was not detected in young mice at P3 but in older mice it was detected in differentiated keratinocytes in some of Hassall's corpuscles (Figure S3).
T17585 32531-32533 NN denotes K1
T17586 32534-32542 NN denotes staining
T17587 32551-32559 VBN denotes detected
T17588 32543-32546 VBD denotes was
T17589 32547-32550 RB denotes not
T17590 32560-32562 IN denotes in
T17591 32563-32568 JJ denotes young
T17592 32569-32573 NNS denotes mice
T17593 32574-32576 IN denotes at
T17594 32577-32579 NN denotes P3
T17595 32580-32583 CC denotes but
T17596 32584-32586 IN denotes in
T17597 32605-32613 VBN denotes detected
T17598 32587-32592 JJR denotes older
T17599 32593-32597 NNS denotes mice
T17600 32598-32600 PRP denotes it
T17601 32601-32604 VBD denotes was
T17602 32614-32616 IN denotes in
T17603 32617-32631 VBN denotes differentiated
T17604 32632-32645 NNS denotes keratinocytes
T17605 32646-32648 IN denotes in
T17606 32649-32653 DT denotes some
T17607 32654-32656 IN denotes of
T17608 32657-32664 NNP denotes Hassall
T17609 32667-32677 NNS denotes corpuscles
T17610 32664-32666 POS denotes 's
T17611 32678-32679 -LRB- denotes (
T17612 32686-32688 NN denotes S3
T17613 32679-32685 NN denotes Figure
T17614 32688-32689 -RRB- denotes )
T17615 32689-32690 . denotes .
T17616 32690-33309 sentence denotes Figure 6 Histological and Immunochemical Examination of Thymus (A–D) P3 normal thymus. (E–G) Mild P3 mutant thymus. (H–K) Severe P3 mutant thymus. (L–O) P13 mutant thymus. Stained with H&E for histology (A, E, H, L), BrdU (B, I, M), β-catenin (C, F, J, N), and K14 (D, G, K, O). (B) Actively dividing thymocytes are visible at the superficial edge of cortex of normal P3 thymus. Note the progression of histological abnormalities in the mutant thymus from mild P3, severe P3 to P13 (A, E, H, L). Scale bars, 20 μm. The histological abnormalities of thymus were evident as early as P3 in KA mutants (Figure 6E and 6H).
T17617 33207-33210 DT denotes The
T17618 33224-33237 NNS denotes abnormalities
T17619 33211-33223 JJ denotes histological
T17620 33248-33252 VBD denotes were
T17621 33238-33240 IN denotes of
T17622 33241-33247 NN denotes thymus
T17623 33253-33260 JJ denotes evident
T17624 33261-33263 RB denotes as
T17625 33264-33269 RB denotes early
T17626 33270-33272 IN denotes as
T17627 33273-33275 NN denotes P3
T17628 33276-33278 IN denotes in
T17629 33279-33281 NN denotes KA
T17630 33282-33289 NNS denotes mutants
T17631 33290-33291 -LRB- denotes (
T17632 33298-33300 NN denotes 6E
T17633 33291-33297 NN denotes Figure
T17634 33301-33304 CC denotes and
T17635 33305-33307 NN denotes 6H
T17636 33307-33308 -RRB- denotes )
T17637 33308-33309 . denotes .
T17638 33309-33473 sentence denotes The thymus was made of two lobules as in the normal mice but the mutant thymus was significantly smaller in size than that of the age-matched controls (Figure 2G).
T17639 33310-33313 DT denotes The
T17640 33314-33320 NN denotes thymus
T17641 33325-33329 VBN denotes made
T17642 33321-33324 VBD denotes was
T17643 33330-33332 IN denotes of
T17644 33333-33336 CD denotes two
T17645 33337-33344 NNS denotes lobules
T17646 33345-33347 IN denotes as
T17647 33348-33350 IN denotes in
T17648 33351-33354 DT denotes the
T17649 33362-33366 NNS denotes mice
T17650 33355-33361 JJ denotes normal
T17651 33367-33370 CC denotes but
T17652 33371-33374 DT denotes the
T17653 33382-33388 NN denotes thymus
T17654 33375-33381 JJ denotes mutant
T17655 33389-33392 VBD denotes was
T17656 33393-33406 RB denotes significantly
T17657 33407-33414 JJR denotes smaller
T17658 33415-33417 IN denotes in
T17659 33418-33422 NN denotes size
T17660 33423-33427 IN denotes than
T17661 33428-33432 DT denotes that
T17662 33433-33435 IN denotes of
T17663 33436-33439 DT denotes the
T17664 33452-33460 NNS denotes controls
T17665 33440-33443 NN denotes age
T17666 33444-33451 JJ denotes matched
T17667 33443-33444 HYPH denotes -
T17668 33461-33462 -LRB- denotes (
T17669 33469-33471 NN denotes 2G
T17670 33462-33468 NN denotes Figure
T17671 33471-33472 -RRB- denotes )
T17672 33472-33473 . denotes .
T17673 33473-33633 sentence denotes Interestingly, variations in the phenotypic severity of the mutant pups at P3 were prominently reflected in the extent of histological abnormalities of thymus.
T17674 33474-33487 RB denotes Interestingly
T17675 33569-33578 VBN denotes reflected
T17676 33487-33489 , denotes ,
T17677 33489-33499 NNS denotes variations
T17678 33500-33502 IN denotes in
T17679 33503-33506 DT denotes the
T17680 33518-33526 NN denotes severity
T17681 33507-33517 JJ denotes phenotypic
T17682 33527-33529 IN denotes of
T17683 33530-33533 DT denotes the
T17684 33541-33545 NNS denotes pups
T17685 33534-33540 JJ denotes mutant
T17686 33546-33548 IN denotes at
T17687 33549-33551 NN denotes P3
T17688 33552-33556 VBD denotes were
T17689 33557-33568 RB denotes prominently
T17690 33579-33581 IN denotes in
T17691 33582-33585 DT denotes the
T17692 33586-33592 NN denotes extent
T17693 33593-33595 IN denotes of
T17694 33596-33608 JJ denotes histological
T17695 33609-33622 NNS denotes abnormalities
T17696 33623-33625 IN denotes of
T17697 33626-33632 NN denotes thymus
T17698 33632-33633 . denotes .
T17699 33633-33874 sentence denotes A P3 KA mutant pup that showed milder phenotype with a comparable body weight to its normal littermates (Figure 2A, M2) showed milder thymus abnormalities (Figure 6E) compared to its more severe mutant littermate (Figure 2A, M1; Figure 6H).
T17700 33634-33635 DT denotes A
T17701 33649-33652 NN denotes pup
T17702 33636-33638 NN denotes P3
T17703 33639-33641 NN denotes KA
T17704 33642-33648 JJ denotes mutant
T17705 33754-33760 VBD denotes showed
T17706 33653-33657 WDT denotes that
T17707 33658-33664 VBD denotes showed
T17708 33665-33671 JJR denotes milder
T17709 33672-33681 NN denotes phenotype
T17710 33682-33686 IN denotes with
T17711 33687-33688 DT denotes a
T17712 33705-33711 NN denotes weight
T17713 33689-33699 JJ denotes comparable
T17714 33700-33704 NN denotes body
T17715 33712-33714 IN denotes to
T17716 33715-33718 PRP$ denotes its
T17717 33726-33737 NNS denotes littermates
T17718 33719-33725 JJ denotes normal
T17719 33738-33739 -LRB- denotes (
T17720 33746-33748 NN denotes 2A
T17721 33739-33745 NN denotes Figure
T17722 33748-33750 , denotes ,
T17723 33750-33752 NN denotes M2
T17724 33752-33753 -RRB- denotes )
T17725 33761-33767 JJR denotes milder
T17726 33775-33788 NNS denotes abnormalities
T17727 33768-33774 NN denotes thymus
T17728 33789-33790 -LRB- denotes (
T17729 33797-33799 NN denotes 6E
T17730 33790-33796 NN denotes Figure
T17731 33799-33800 -RRB- denotes )
T17732 33801-33809 VBN denotes compared
T17733 33810-33812 IN denotes to
T17734 33813-33816 PRP$ denotes its
T17735 33836-33846 NN denotes littermate
T17736 33817-33821 RBR denotes more
T17737 33822-33828 JJ denotes severe
T17738 33829-33835 JJ denotes mutant
T17739 33847-33848 -LRB- denotes (
T17740 33855-33857 NN denotes 2A
T17741 33848-33854 NN denotes Figure
T17742 33857-33859 , denotes ,
T17743 33859-33861 NN denotes M1
T17744 33861-33862 : denotes ;
T17745 33863-33869 NN denotes Figure
T17746 33870-33872 NN denotes 6H
T17747 33872-33873 -RRB- denotes )
T17748 33873-33874 . denotes .
T17749 33874-34132 sentence denotes The milder P3 mutant thymus was already much smaller in size compared to those of normal littermates (data not shown) but two epithelial compartments of thymus were histologically still distinguishable, with colonization of thymocytes evident in the cortex.
T17750 33875-33878 DT denotes The
T17751 33896-33902 NN denotes thymus
T17752 33879-33885 JJR denotes milder
T17753 33886-33888 NN denotes P3
T17754 33889-33895 JJ denotes mutant
T17755 33903-33906 VBD denotes was
T17756 33907-33914 RB denotes already
T17757 33915-33919 RB denotes much
T17758 33920-33927 JJR denotes smaller
T17759 33928-33930 IN denotes in
T17760 33931-33935 NN denotes size
T17761 33936-33944 VBN denotes compared
T17762 33945-33947 IN denotes to
T17763 33948-33953 DT denotes those
T17764 33954-33956 IN denotes of
T17765 33957-33963 JJ denotes normal
T17766 33964-33975 NNS denotes littermates
T17767 33976-33977 -LRB- denotes (
T17768 33986-33991 VBN denotes shown
T17769 33977-33981 NNS denotes data
T17770 33982-33985 RB denotes not
T17771 33991-33992 -RRB- denotes )
T17772 33993-33996 CC denotes but
T17773 33997-34000 CD denotes two
T17774 34012-34024 NNS denotes compartments
T17775 34001-34011 JJ denotes epithelial
T17776 34035-34039 VBD denotes were
T17777 34025-34027 IN denotes of
T17778 34028-34034 NN denotes thymus
T17779 34040-34054 RB denotes histologically
T17780 34055-34060 RB denotes still
T17781 34061-34076 JJ denotes distinguishable
T17782 34076-34078 , denotes ,
T17783 34078-34082 IN denotes with
T17784 34110-34117 JJ denotes evident
T17785 34083-34095 NN denotes colonization
T17786 34096-34098 IN denotes of
T17787 34099-34109 NNS denotes thymocytes
T17788 34118-34120 IN denotes in
T17789 34121-34124 DT denotes the
T17790 34125-34131 NN denotes cortex
T17791 34131-34132 . denotes .
T17792 34132-34465 sentence denotes However, there were small populations of lightly stained cells by H&E extending from the edge of the outer cortex towards inner medulla (Figure 6E), and these cells showed intense nuclear β-catenin staining whereas the rest of the medullary cells showed diffuse β-catenin staining pattern similar to that of the control (Figure 6F).
T17793 34133-34140 RB denotes However
T17794 34148-34152 VBD denotes were
T17795 34140-34142 , denotes ,
T17796 34142-34147 EX denotes there
T17797 34153-34158 JJ denotes small
T17798 34159-34170 NNS denotes populations
T17799 34171-34173 IN denotes of
T17800 34174-34181 RB denotes lightly
T17801 34182-34189 VBN denotes stained
T17802 34190-34195 NNS denotes cells
T17803 34196-34198 IN denotes by
T17804 34199-34200 NN denotes H
T17805 34200-34201 CC denotes &
T17806 34201-34202 NN denotes E
T17807 34203-34212 VBG denotes extending
T17808 34213-34217 IN denotes from
T17809 34218-34221 DT denotes the
T17810 34222-34226 NN denotes edge
T17811 34227-34229 IN denotes of
T17812 34230-34233 DT denotes the
T17813 34240-34246 NN denotes cortex
T17814 34234-34239 JJ denotes outer
T17815 34247-34254 IN denotes towards
T17816 34255-34260 JJ denotes inner
T17817 34261-34268 NN denotes medulla
T17818 34269-34270 -LRB- denotes (
T17819 34277-34279 NN denotes 6E
T17820 34270-34276 NN denotes Figure
T17821 34279-34280 -RRB- denotes )
T17822 34280-34282 , denotes ,
T17823 34282-34285 CC denotes and
T17824 34286-34291 DT denotes these
T17825 34292-34297 NNS denotes cells
T17826 34298-34304 VBD denotes showed
T17827 34305-34312 JJ denotes intense
T17828 34331-34339 NN denotes staining
T17829 34313-34320 JJ denotes nuclear
T17830 34321-34322 NN denotes β
T17831 34323-34330 NN denotes catenin
T17832 34322-34323 HYPH denotes -
T17833 34340-34347 IN denotes whereas
T17834 34380-34386 VBD denotes showed
T17835 34348-34351 DT denotes the
T17836 34352-34356 NN denotes rest
T17837 34357-34359 IN denotes of
T17838 34360-34363 DT denotes the
T17839 34374-34379 NNS denotes cells
T17840 34364-34373 JJ denotes medullary
T17841 34387-34394 JJ denotes diffuse
T17842 34414-34421 NN denotes pattern
T17843 34395-34396 NN denotes β
T17844 34397-34404 NN denotes catenin
T17845 34396-34397 HYPH denotes -
T17846 34405-34413 NN denotes staining
T17847 34422-34429 JJ denotes similar
T17848 34430-34432 IN denotes to
T17849 34433-34437 DT denotes that
T17850 34438-34440 IN denotes of
T17851 34441-34444 DT denotes the
T17852 34445-34452 NN denotes control
T17853 34453-34454 -LRB- denotes (
T17854 34461-34463 NN denotes 6F
T17855 34454-34460 NN denotes Figure
T17856 34463-34464 -RRB- denotes )
T17857 34464-34465 . denotes .
T17858 34465-34581 sentence denotes Localization of K14 was limited to a few cells in the medulla and some overlapped with K8 localization (Figure 6G).
T17859 34466-34478 NN denotes Localization
T17860 34490-34497 VBN denotes limited
T17861 34479-34481 IN denotes of
T17862 34482-34485 NN denotes K14
T17863 34486-34489 VBD denotes was
T17864 34498-34500 IN denotes to
T17865 34501-34502 DT denotes a
T17866 34507-34512 NNS denotes cells
T17867 34503-34506 JJ denotes few
T17868 34513-34515 IN denotes in
T17869 34516-34519 DT denotes the
T17870 34520-34527 NN denotes medulla
T17871 34528-34531 CC denotes and
T17872 34532-34536 DT denotes some
T17873 34537-34547 VBN denotes overlapped
T17874 34548-34552 IN denotes with
T17875 34553-34555 NN denotes K8
T17876 34556-34568 NN denotes localization
T17877 34569-34570 -LRB- denotes (
T17878 34577-34579 NN denotes 6G
T17879 34570-34576 NN denotes Figure
T17880 34579-34580 -RRB- denotes )
T17881 34580-34581 . denotes .
T17882 34581-34773 sentence denotes In the other P3 mutant thymus the distinct thymic epithelial compartments have been lost completely, and only a few lymphocytes were remaining at the edges and some in the middle (Figure 6H).
T17883 34582-34584 IN denotes In
T17884 34666-34670 VBN denotes lost
T17885 34585-34588 DT denotes the
T17886 34605-34611 NN denotes thymus
T17887 34589-34594 JJ denotes other
T17888 34595-34597 NN denotes P3
T17889 34598-34604 JJ denotes mutant
T17890 34612-34615 DT denotes the
T17891 34643-34655 NNS denotes compartments
T17892 34616-34624 JJ denotes distinct
T17893 34625-34631 JJ denotes thymic
T17894 34632-34642 JJ denotes epithelial
T17895 34656-34660 VBP denotes have
T17896 34661-34665 VBN denotes been
T17897 34671-34681 RB denotes completely
T17898 34681-34683 , denotes ,
T17899 34683-34686 CC denotes and
T17900 34687-34691 RB denotes only
T17901 34698-34709 NNS denotes lymphocytes
T17902 34692-34693 DT denotes a
T17903 34694-34697 JJ denotes few
T17904 34715-34724 VBG denotes remaining
T17905 34710-34714 VBD denotes were
T17906 34725-34727 IN denotes at
T17907 34728-34731 DT denotes the
T17908 34732-34737 NNS denotes edges
T17909 34738-34741 CC denotes and
T17910 34742-34746 DT denotes some
T17911 34747-34749 IN denotes in
T17912 34750-34753 DT denotes the
T17913 34754-34760 JJ denotes middle
T17914 34761-34762 -LRB- denotes (
T17915 34769-34771 NN denotes 6H
T17916 34762-34768 NN denotes Figure
T17917 34771-34772 -RRB- denotes )
T17918 34772-34773 . denotes .
T17919 34773-34957 sentence denotes Proliferative activities were no longer observed in thymocytes as prominently as in the normal thymus, but the epithelial cells seemed to be forming concentric structures (Figure 6I).
T17920 34774-34787 JJ denotes Proliferative
T17921 34788-34798 NNS denotes activities
T17922 34814-34822 VBN denotes observed
T17923 34799-34803 VBD denotes were
T17924 34804-34806 RB denotes no
T17925 34807-34813 RBR denotes longer
T17926 34823-34825 IN denotes in
T17927 34826-34836 NNS denotes thymocytes
T17928 34837-34839 RB denotes as
T17929 34840-34851 RB denotes prominently
T17930 34852-34854 IN denotes as
T17931 34855-34857 IN denotes in
T17932 34858-34861 DT denotes the
T17933 34869-34875 NN denotes thymus
T17934 34862-34868 JJ denotes normal
T17935 34875-34877 , denotes ,
T17936 34877-34880 CC denotes but
T17937 34881-34884 DT denotes the
T17938 34896-34901 NNS denotes cells
T17939 34885-34895 JJ denotes epithelial
T17940 34902-34908 VBD denotes seemed
T17941 34909-34911 TO denotes to
T17942 34915-34922 VBG denotes forming
T17943 34912-34914 VB denotes be
T17944 34923-34933 JJ denotes concentric
T17945 34934-34944 NNS denotes structures
T17946 34945-34946 -LRB- denotes (
T17947 34953-34955 NN denotes 6I
T17948 34946-34952 NN denotes Figure
T17949 34955-34956 -RRB- denotes )
T17950 34956-34957 . denotes .
T17951 34957-35108 sentence denotes Unlike in the normal or mild mutant thymi, the severe P3 mutant thymus showed extensive K14 expression that overlapped with K8 expression (Figure 6K).
T17952 34958-34964 IN denotes Unlike
T17953 35029-35035 VBD denotes showed
T17954 34965-34967 IN denotes in
T17955 34968-34971 DT denotes the
T17956 34994-34999 NNS denotes thymi
T17957 34972-34978 JJ denotes normal
T17958 34979-34981 CC denotes or
T17959 34982-34986 JJ denotes mild
T17960 34987-34993 JJ denotes mutant
T17961 34999-35001 , denotes ,
T17962 35001-35004 DT denotes the
T17963 35022-35028 NN denotes thymus
T17964 35005-35011 JJ denotes severe
T17965 35012-35014 NN denotes P3
T17966 35015-35021 JJ denotes mutant
T17967 35036-35045 JJ denotes extensive
T17968 35050-35060 NN denotes expression
T17969 35046-35049 NN denotes K14
T17970 35061-35065 WDT denotes that
T17971 35066-35076 VBD denotes overlapped
T17972 35077-35081 IN denotes with
T17973 35082-35084 NN denotes K8
T17974 35085-35095 NN denotes expression
T17975 35096-35097 -LRB- denotes (
T17976 35104-35106 NN denotes 6K
T17977 35097-35103 NN denotes Figure
T17978 35106-35107 -RRB- denotes )
T17979 35107-35108 . denotes .
T17980 35108-35303 sentence denotes These cells were more like basal cells of the skin than TECs and were adjacent to the most immature looking cells that were showing strong nuclear and cytoplasmic β-catenin staining (Figure 6J).
T17981 35109-35114 DT denotes These
T17982 35115-35120 NNS denotes cells
T17983 35121-35125 VBD denotes were
T17984 35126-35130 RBR denotes more
T17985 35131-35135 IN denotes like
T17986 35136-35141 JJ denotes basal
T17987 35142-35147 NNS denotes cells
T17988 35148-35150 IN denotes of
T17989 35151-35154 DT denotes the
T17990 35155-35159 NN denotes skin
T17991 35160-35164 IN denotes than
T17992 35165-35169 NNS denotes TECs
T17993 35170-35173 CC denotes and
T17994 35174-35178 VBD denotes were
T17995 35179-35187 JJ denotes adjacent
T17996 35188-35190 IN denotes to
T17997 35191-35194 DT denotes the
T17998 35217-35222 NNS denotes cells
T17999 35195-35199 RBS denotes most
T18000 35200-35208 JJ denotes immature
T18001 35209-35216 VBG denotes looking
T18002 35223-35227 WDT denotes that
T18003 35233-35240 VBG denotes showing
T18004 35228-35232 VBD denotes were
T18005 35241-35247 JJ denotes strong
T18006 35282-35290 NN denotes staining
T18007 35248-35255 JJ denotes nuclear
T18008 35256-35259 CC denotes and
T18009 35260-35271 JJ denotes cytoplasmic
T18010 35272-35273 NN denotes β
T18011 35274-35281 NN denotes catenin
T18012 35273-35274 HYPH denotes -
T18013 35291-35292 -LRB- denotes (
T18014 35299-35301 NN denotes 6J
T18015 35292-35298 NN denotes Figure
T18016 35301-35302 -RRB- denotes )
T18017 35302-35303 . denotes .
T18018 35303-35400 sentence denotes The nuclear staining of β-catenin was not observed in the normal age-matched thymus (Figure 6C).
T18019 35304-35307 DT denotes The
T18020 35316-35324 NN denotes staining
T18021 35308-35315 JJ denotes nuclear
T18022 35346-35354 VBN denotes observed
T18023 35325-35327 IN denotes of
T18024 35328-35329 NN denotes β
T18025 35330-35337 NN denotes catenin
T18026 35329-35330 HYPH denotes -
T18027 35338-35341 VBD denotes was
T18028 35342-35345 RB denotes not
T18029 35355-35357 IN denotes in
T18030 35358-35361 DT denotes the
T18031 35381-35387 NN denotes thymus
T18032 35362-35368 JJ denotes normal
T18033 35369-35372 NN denotes age
T18034 35373-35380 JJ denotes matched
T18035 35372-35373 HYPH denotes -
T18036 35388-35389 -LRB- denotes (
T18037 35396-35398 NN denotes 6C
T18038 35389-35395 NN denotes Figure
T18039 35398-35399 -RRB- denotes )
T18040 35399-35400 . denotes .
T18041 35400-35498 sentence denotes Most notably, the K14 and β-catenin staining patterns were mutually exclusive (Figure 6J and 6K).
T18042 35401-35405 RBS denotes Most
T18043 35406-35413 RB denotes notably
T18044 35455-35459 VBD denotes were
T18045 35413-35415 , denotes ,
T18046 35415-35418 DT denotes the
T18047 35446-35454 NNS denotes patterns
T18048 35419-35422 NN denotes K14
T18049 35423-35426 CC denotes and
T18050 35427-35428 NN denotes β
T18051 35429-35436 NN denotes catenin
T18052 35428-35429 HYPH denotes -
T18053 35437-35445 NN denotes staining
T18054 35460-35468 RB denotes mutually
T18055 35469-35478 JJ denotes exclusive
T18056 35479-35480 -LRB- denotes (
T18057 35487-35489 NN denotes 6J
T18058 35480-35486 NN denotes Figure
T18059 35490-35493 CC denotes and
T18060 35494-35496 NN denotes 6K
T18061 35496-35497 -RRB- denotes )
T18062 35497-35498 . denotes .
T18063 35498-35722 sentence denotes At P10–P13, the mutant thymus consisted of numerous enlarged Hassall's corpuscle–like structures, made of arrays of K14- and K8-expressing keratinizing epithelial cells surrounding large keratin deposits (Figure 6L and 6O).
T18064 35499-35501 IN denotes At
T18065 35529-35538 VBD denotes consisted
T18066 35502-35505 NN denotes P10
T18067 35505-35506 SYM denotes
T18068 35506-35509 NN denotes P13
T18069 35509-35511 , denotes ,
T18070 35511-35514 DT denotes the
T18071 35522-35528 NN denotes thymus
T18072 35515-35521 JJ denotes mutant
T18073 35539-35541 IN denotes of
T18074 35542-35550 JJ denotes numerous
T18075 35585-35595 NNS denotes structures
T18076 35551-35559 VBN denotes enlarged
T18077 35560-35567 NNP denotes Hassall
T18078 35567-35569 POS denotes 's
T18079 35570-35579 NN denotes corpuscle
T18080 35580-35584 JJ denotes like
T18081 35579-35580 HYPH denotes
T18082 35595-35597 , denotes ,
T18083 35597-35601 VBN denotes made
T18084 35602-35604 IN denotes of
T18085 35605-35611 NNS denotes arrays
T18086 35612-35614 IN denotes of
T18087 35615-35618 NN denotes K14
T18088 35627-35637 VBG denotes expressing
T18089 35618-35619 HYPH denotes -
T18090 35620-35623 CC denotes and
T18091 35624-35626 NN denotes K8
T18092 35626-35627 HYPH denotes -
T18093 35662-35667 NNS denotes cells
T18094 35638-35650 VBG denotes keratinizing
T18095 35651-35661 JJ denotes epithelial
T18096 35668-35679 VBG denotes surrounding
T18097 35680-35685 JJ denotes large
T18098 35694-35702 NNS denotes deposits
T18099 35686-35693 NN denotes keratin
T18100 35703-35704 -LRB- denotes (
T18101 35711-35713 NN denotes 6L
T18102 35704-35710 NN denotes Figure
T18103 35714-35717 CC denotes and
T18104 35718-35720 NN denotes 6O
T18105 35720-35721 -RRB- denotes )
T18106 35721-35722 . denotes .
T18107 35722-35879 sentence denotes There were numerous neutrophils and macrophages infiltrating the thymus in response to these keratins; hence, these structures could be called pyogranuloma.
T18108 35723-35728 EX denotes There
T18109 35729-35733 VBD denotes were
T18110 35859-35865 VBN denotes called
T18111 35734-35742 JJ denotes numerous
T18112 35743-35754 NNS denotes neutrophils
T18113 35755-35758 CC denotes and
T18114 35759-35770 NNS denotes macrophages
T18115 35771-35783 VBG denotes infiltrating
T18116 35784-35787 DT denotes the
T18117 35788-35794 NN denotes thymus
T18118 35795-35797 IN denotes in
T18119 35798-35806 NN denotes response
T18120 35807-35809 IN denotes to
T18121 35810-35815 DT denotes these
T18122 35816-35824 NNS denotes keratins
T18123 35824-35825 : denotes ;
T18124 35826-35831 RB denotes hence
T18125 35831-35833 , denotes ,
T18126 35833-35838 DT denotes these
T18127 35839-35849 NNS denotes structures
T18128 35850-35855 MD denotes could
T18129 35856-35858 VB denotes be
T18130 35866-35878 NN denotes pyogranuloma
T18131 35878-35879 . denotes .
T18132 35879-36096 sentence denotes Varying degrees of differentiation-specific markers depending on the age of mice, in this case K1 and involucrin that are normally present only in Hassall's corpuscles, were also detected in mutant thymi (Figure S3).
T18133 35880-35887 VBG denotes Varying
T18134 35888-35895 NNS denotes degrees
T18135 36059-36067 VBN denotes detected
T18136 35896-35898 IN denotes of
T18137 35899-35914 NN denotes differentiation
T18138 35915-35923 JJ denotes specific
T18139 35914-35915 HYPH denotes -
T18140 35924-35931 NNS denotes markers
T18141 35932-35941 VBG denotes depending
T18142 35942-35944 IN denotes on
T18143 35945-35948 DT denotes the
T18144 35949-35952 NN denotes age
T18145 35953-35955 IN denotes of
T18146 35956-35960 NNS denotes mice
T18147 35960-35962 , denotes ,
T18148 35962-35964 IN denotes in
T18149 35975-35977 NN denotes K1
T18150 35965-35969 DT denotes this
T18151 35970-35974 NN denotes case
T18152 35978-35981 CC denotes and
T18153 35982-35992 NN denotes involucrin
T18154 35993-35997 WDT denotes that
T18155 35998-36001 VBP denotes are
T18156 36002-36010 RB denotes normally
T18157 36011-36018 JJ denotes present
T18158 36019-36023 RB denotes only
T18159 36024-36026 IN denotes in
T18160 36027-36034 NNP denotes Hassall
T18161 36037-36047 NNS denotes corpuscles
T18162 36034-36036 POS denotes 's
T18163 36047-36049 , denotes ,
T18164 36049-36053 VBD denotes were
T18165 36054-36058 RB denotes also
T18166 36068-36070 IN denotes in
T18167 36071-36077 JJ denotes mutant
T18168 36078-36083 NNS denotes thymi
T18169 36084-36085 -LRB- denotes (
T18170 36092-36094 NN denotes S3
T18171 36085-36091 NN denotes Figure
T18172 36094-36095 -RRB- denotes )
T18173 36095-36096 . denotes .
T18174 36096-36141 sentence denotes In these mice no thymocytes were detectable.
T18175 36097-36099 IN denotes In
T18176 36125-36129 VBD denotes were
T18177 36100-36105 DT denotes these
T18178 36106-36110 NNS denotes mice
T18179 36111-36113 DT denotes no
T18180 36114-36124 NNS denotes thymocytes
T18181 36130-36140 JJ denotes detectable
T18182 36140-36141 . denotes .
T18183 36141-36289 sentence denotes BrdU incorporation was only observed in very few keratinizing epithelial cells, looking somewhat similar to the pattern of mature skin (Figure 6M).
T18184 36142-36146 NN denotes BrdU
T18185 36147-36160 NN denotes incorporation
T18186 36222-36229 VBG denotes looking
T18187 36161-36164 VBD denotes was
T18188 36165-36169 RB denotes only
T18189 36170-36178 VBN denotes observed
T18190 36179-36181 IN denotes in
T18191 36182-36186 RB denotes very
T18192 36187-36190 JJ denotes few
T18193 36215-36220 NNS denotes cells
T18194 36191-36203 VBG denotes keratinizing
T18195 36204-36214 JJ denotes epithelial
T18196 36220-36222 , denotes ,
T18197 36230-36238 RB denotes somewhat
T18198 36239-36246 JJ denotes similar
T18199 36247-36249 IN denotes to
T18200 36250-36253 DT denotes the
T18201 36254-36261 NN denotes pattern
T18202 36262-36264 IN denotes of
T18203 36265-36271 JJ denotes mature
T18204 36272-36276 NN denotes skin
T18205 36277-36278 -LRB- denotes (
T18206 36285-36287 NN denotes 6M
T18207 36278-36284 NN denotes Figure
T18208 36287-36288 -RRB- denotes )
T18209 36288-36289 . denotes .
T18210 36289-36455 sentence denotes The diffuse expression of β-catenin was also present in these epithelial cells, and at this age fewer cells were positive for nuclear β-catenin staining (Figure 6N).
T18211 36290-36293 DT denotes The
T18212 36302-36312 NN denotes expression
T18213 36294-36301 JJ denotes diffuse
T18214 36326-36329 VBD denotes was
T18215 36313-36315 IN denotes of
T18216 36316-36317 NN denotes β
T18217 36318-36325 NN denotes catenin
T18218 36317-36318 HYPH denotes -
T18219 36330-36334 RB denotes also
T18220 36335-36342 JJ denotes present
T18221 36343-36345 IN denotes in
T18222 36346-36351 DT denotes these
T18223 36363-36368 NNS denotes cells
T18224 36352-36362 JJ denotes epithelial
T18225 36368-36370 , denotes ,
T18226 36370-36373 CC denotes and
T18227 36374-36376 IN denotes at
T18228 36398-36402 VBD denotes were
T18229 36377-36381 DT denotes this
T18230 36382-36385 NN denotes age
T18231 36386-36391 JJR denotes fewer
T18232 36392-36397 NNS denotes cells
T18233 36403-36411 JJ denotes positive
T18234 36412-36415 IN denotes for
T18235 36416-36423 JJ denotes nuclear
T18236 36434-36442 NN denotes staining
T18237 36424-36425 NN denotes β
T18238 36426-36433 NN denotes catenin
T18239 36425-36426 HYPH denotes -
T18240 36443-36444 -LRB- denotes (
T18241 36451-36453 NN denotes 6N
T18242 36444-36450 NN denotes Figure
T18243 36453-36454 -RRB- denotes )
T18244 36454-36455 . denotes .
T18245 36455-36616 sentence denotes As in the younger mutant mice, however, nuclear localization of β-catenin was only observed in K14-negative cells that looked like undifferentiated basal cells.
T18246 36456-36458 IN denotes As
T18247 36539-36547 VBN denotes observed
T18248 36459-36461 IN denotes in
T18249 36462-36465 DT denotes the
T18250 36481-36485 NNS denotes mice
T18251 36466-36473 JJR denotes younger
T18252 36474-36480 JJ denotes mutant
T18253 36485-36487 , denotes ,
T18254 36487-36494 RB denotes however
T18255 36494-36496 , denotes ,
T18256 36496-36503 JJ denotes nuclear
T18257 36504-36516 NN denotes localization
T18258 36517-36519 IN denotes of
T18259 36520-36521 NN denotes β
T18260 36522-36529 NN denotes catenin
T18261 36521-36522 HYPH denotes -
T18262 36530-36533 VBD denotes was
T18263 36534-36538 RB denotes only
T18264 36548-36550 IN denotes in
T18265 36551-36554 NN denotes K14
T18266 36555-36563 JJ denotes negative
T18267 36554-36555 HYPH denotes -
T18268 36564-36569 NNS denotes cells
T18269 36570-36574 WDT denotes that
T18270 36575-36581 VBD denotes looked
T18271 36582-36586 IN denotes like
T18272 36587-36603 JJ denotes undifferentiated
T18273 36610-36615 NNS denotes cells
T18274 36604-36609 JJ denotes basal
T18275 36615-36616 . denotes .
T18276 36616-36875 sentence denotes In older P17 mice, the histopathology and keratin expression pattern of the mutant thymus was similar to that of P13 except for the fact that β-catenin expression became increasingly diffuse and appeared to colocalize with K8/K14 expression (data not shown).
T18277 36617-36619 IN denotes In
T18278 36707-36710 VBD denotes was
T18279 36620-36625 JJR denotes older
T18280 36630-36634 NNS denotes mice
T18281 36626-36629 NN denotes P17
T18282 36634-36636 , denotes ,
T18283 36636-36639 DT denotes the
T18284 36640-36654 NN denotes histopathology
T18285 36655-36658 CC denotes and
T18286 36659-36666 NN denotes keratin
T18287 36678-36685 NN denotes pattern
T18288 36667-36677 NN denotes expression
T18289 36686-36688 IN denotes of
T18290 36689-36692 DT denotes the
T18291 36700-36706 NN denotes thymus
T18292 36693-36699 JJ denotes mutant
T18293 36711-36718 JJ denotes similar
T18294 36719-36721 IN denotes to
T18295 36722-36726 DT denotes that
T18296 36727-36729 IN denotes of
T18297 36730-36733 NN denotes P13
T18298 36734-36740 IN denotes except
T18299 36741-36744 IN denotes for
T18300 36745-36748 DT denotes the
T18301 36749-36753 NN denotes fact
T18302 36754-36758 IN denotes that
T18303 36780-36786 VBD denotes became
T18304 36759-36760 NN denotes β
T18305 36761-36768 NN denotes catenin
T18306 36760-36761 HYPH denotes -
T18307 36769-36779 NN denotes expression
T18308 36787-36799 RB denotes increasingly
T18309 36800-36807 JJ denotes diffuse
T18310 36808-36811 CC denotes and
T18311 36812-36820 VBD denotes appeared
T18312 36821-36823 TO denotes to
T18313 36824-36834 VB denotes colocalize
T18314 36835-36839 IN denotes with
T18315 36840-36842 NN denotes K8
T18316 36843-36846 NN denotes K14
T18317 36842-36843 HYPH denotes /
T18318 36847-36857 NN denotes expression
T18319 36858-36859 -LRB- denotes (
T18320 36868-36873 VBN denotes shown
T18321 36859-36863 NNS denotes data
T18322 36864-36867 RB denotes not
T18323 36873-36874 -RRB- denotes )
T18324 36874-36875 . denotes .
T18325 36875-36944 sentence denotes This coincided with fewer immature cells in the older mutant thymus.
T18326 36876-36880 DT denotes This
T18327 36881-36890 VBD denotes coincided
T18328 36891-36895 IN denotes with
T18329 36896-36901 JJR denotes fewer
T18330 36911-36916 NNS denotes cells
T18331 36902-36910 JJ denotes immature
T18332 36917-36919 IN denotes in
T18333 36920-36923 DT denotes the
T18334 36937-36943 NN denotes thymus
T18335 36924-36929 JJR denotes older
T18336 36930-36936 JJ denotes mutant
T18337 36943-36944 . denotes .
T18338 36944-37229 sentence denotes Collectively, these results suggest that loss of Apc and consequent stabilization of β-catenin in K14-expressing TECs lead to their aberrant proliferation and differentiation to keratinocytes, causing massive squamous metaplasia, rather than to form either medullary or cortical TECs.
T18339 36945-36957 RB denotes Collectively
T18340 36973-36980 VBP denotes suggest
T18341 36957-36959 , denotes ,
T18342 36959-36964 DT denotes these
T18343 36965-36972 NNS denotes results
T18344 36981-36985 IN denotes that
T18345 37063-37067 VBP denotes lead
T18346 36986-36990 NN denotes loss
T18347 36991-36993 IN denotes of
T18348 36994-36997 NN denotes Apc
T18349 36998-37001 CC denotes and
T18350 37002-37012 JJ denotes consequent
T18351 37013-37026 NN denotes stabilization
T18352 37027-37029 IN denotes of
T18353 37030-37031 NN denotes β
T18354 37032-37039 NN denotes catenin
T18355 37031-37032 HYPH denotes -
T18356 37040-37042 IN denotes in
T18357 37043-37046 NN denotes K14
T18358 37047-37057 VBG denotes expressing
T18359 37046-37047 HYPH denotes -
T18360 37058-37062 NNS denotes TECs
T18361 37068-37070 IN denotes to
T18362 37071-37076 PRP$ denotes their
T18363 37086-37099 NN denotes proliferation
T18364 37077-37085 JJ denotes aberrant
T18365 37100-37103 CC denotes and
T18366 37104-37119 NN denotes differentiation
T18367 37120-37122 IN denotes to
T18368 37123-37136 NNS denotes keratinocytes
T18369 37136-37138 , denotes ,
T18370 37138-37145 VBG denotes causing
T18371 37146-37153 JJ denotes massive
T18372 37163-37173 NN denotes metaplasia
T18373 37154-37162 JJ denotes squamous
T18374 37173-37175 , denotes ,
T18375 37175-37181 IN denotes rather
T18376 37182-37186 IN denotes than
T18377 37187-37189 TO denotes to
T18378 37190-37194 VB denotes form
T18379 37195-37201 CC denotes either
T18380 37202-37211 JJ denotes medullary
T18381 37224-37228 NNS denotes TECs
T18382 37212-37214 CC denotes or
T18383 37215-37223 JJ denotes cortical
T18384 37228-37229 . denotes .
T18385 37229-37350 sentence denotes Loss of proper TEC compartments consequently resulted in loss of thymocytes for maturation and the mice to be “athymic.”
T18386 37230-37234 NN denotes Loss
T18387 37275-37283 VBD denotes resulted
T18388 37235-37237 IN denotes of
T18389 37238-37244 JJ denotes proper
T18390 37249-37261 NNS denotes compartments
T18391 37245-37248 NN denotes TEC
T18392 37262-37274 RB denotes consequently
T18393 37284-37286 IN denotes in
T18394 37287-37291 NN denotes loss
T18395 37292-37294 IN denotes of
T18396 37295-37305 NNS denotes thymocytes
T18397 37306-37309 IN denotes for
T18398 37310-37320 NN denotes maturation
T18399 37321-37324 CC denotes and
T18400 37325-37328 DT denotes the
T18401 37329-37333 NNS denotes mice
T18402 37337-37339 VB denotes be
T18403 37334-37336 TO denotes to
T18404 37340-37341 `` denotes
T18405 37341-37348 JJ denotes athymic
T18406 37348-37349 . denotes .
T18407 37349-37350 '' denotes
T19064 0-37367 NN denotes Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus Role of APC in Skin and Its Appendages Abstract The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre–mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; ApcCKO/CKO mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial–mesenchymal interactions for their development. Synopsis Patients with familial adenomatous polyposis (FAP) and its variant, Gardner's syndrome, will develop hundreds of colorectal polyps. It is a heritable disease that is linked to a genetic mutation in the tumor suppressor gene APC (adenomatous polyposis coli). These individuals also develop extracolonic symptoms, among which are congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, epidermoid cysts, disorders of the maxillary and skeletal bones, and dental abnormalities, suggesting the importance of APC functions in these organs. To understand the role of Apc in development and in organs other than intestine, we generated Apc mutant mice that can conditionally delete the gene when exposed to Cre recombinase. These mice were mated with K14 (Keratin 14)–cre mice that express Cre recombinase in skin and its appendages. The authors found that the mutant mice that have lost Apc in K14-cre transgene–expressing tissues were viable, but had stunted growth and died before weaning. These mutant mice showed developmental abnormalities not only in skin but also in many epithelial-derived tissues, including teeth and thymus. This work demonstrates the importance of Apc in development of many organs, and provides new insights into diagnosis and management of patients with APC mutations. Introduction Adenomatous polyposis coli (APC) is a member of the Wnt signaling pathway and one of its known functions is to regulate the levels of β-catenin. Alterations in β-catenin regulation are very common in human tumors [1]. Loss of APC is associated with stabilization of the cytosolic β-catenin that ultimately results in its migration to the nucleus and activating a cascade of events leading to tumorigenesis. APC also interacts with a multitude of other cellular proteins, including axin-2 (AXIN2), plakoglobin (JUP), Asef (ARHGEF4), kinesin superfamily–associated protein 3 (KIFAP3), EB1 (MAPRE1), microtubules, and the human homolog of Drosophila discs large (DLG1). These interactions suggest that APC can potentially regulate many cellular functions, including intercellular adhesion, cytoskeletal organization, regulation of plakoglobin levels, regulation of the cell cycle and apoptosis, orientation of asymmetric stem cell division, and control of cell polarization [2,3]. APC is a tumor suppressor gene. Somatic mutations in APC are frequently found in many sporadic tumors of the colon and rectum. Autosomal dominant germline mutations in APC cause familial adenomatous polypois (FAP) and its variant, Gardner syndrome. FAP patients are characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer in the third and fourth decades of life [4,5]. In addition to colorectal neoplams, these individuals can develop extracolonic symptoms, among which are upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, disorders of the maxillary and skeletal bones, and dental abnormalities [6], suggesting the importance of APC gene functions in these organ systems. Although the role of APC in the initiation of human colorectal cancer is well established, its role in other tissue and developmental processes are not well understood. Given the importance of regulation of Wnt signaling in embryonic pattern formation and morphogenesis of many organs, mechanistic understanding of APC in development and in extracolonic tissues becomes critical to better assess potential adverse events in humans. One approach to understand the role of Apc in development is to develop mice with an inactivating Apc mutation. Several genetically modified mouse strains for Apc have been described [7–10]. Most of these models, in the heterozygous state, show a gastrointestinal and other tumor predisposition phenotype [7–10]. Mouse embryos that are homozygous for the genetic modification die during embryogenesis, and some of the models do not survive beyond gastrulation [8,11]. An alternate approach to understand the role of Apc in development and/or in specific tissues is to generate a mouse strain that carries a conditionally modified allele and mate it with a mouse strain that facilitates the modification of the conditional allele in specific cell lineages. To assess the role of Apc in different stages of life systematically, we generated mice containing a conditional knockout (CKO) mutant allele of Apc (ApcCKO). These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. We report here that K14 promoter-driven loss of Apc resulted in aberrant development of several organs that require inductive epithelial–mesenchymal interactions, including hair follicle, teeth, and thymus, and resulted in neonatal death in mice. We found that Apc plays a crucial role in determinations of cell fates during the embryonic development, possibly via temporal and tissue-specific regulation of β-catenin levels in the skin, its appendages, and in the thymus. Results Generation of the ApcCKO and ApcΔ580 Mice To investigate the role of Apc in development of skin and its appendages, we used the Cre/loxP technology to introduce a conditional mutation of the Apc gene in mice. We constructed embryonic stem (ES) cells and mice carrying an Apc allele harboring both a pair of loxP sites flanking Apc exon 14 and a pair of FLP recognition target (FRT) sites flanking PGK-neomycin selection cassette by recombineering [12,13] (Figure 1A, ApcCKON allele, N for neomycin cassette). A PGK-neomycin cassette was inserted in the same transcriptional orientation as Apc in intron 14 of the endogenous gene. The loxP and FRT sites were used to aid unidirectional recombination [12,13]. Two mouse lines containing the same modification were generated from two independent ES clones to ensure that these two lines behave in the same way. These ApcCKON/+ mice were crossed with FLPe-deleter to generate ApcCKO/+ mice that were heterozygous for the final Apc conditional (ApcCKO) allele that removed the PGK-neomycin cassette and contains only the loxP sites in the introns flanking exon 14. To assess the effect of deleting exon 14 in mice, both lines of ApcCKO/+ mice were crossed with the Cre-deleter to generate the germline knockout line of Apc, designated ApcΔ580/+. The mutant allele (ApcΔ580) lacks exon 14 (Figure 1A). The transcript from loss of exon 14 results in a shift in the normal reading frame, resulting in a premature chain termination codon which, if utilized, would result in a truncated polypeptide that is 605 aa in length, of which the first 580 aa correspond to the normal Apc protein. Figure 1 Generation of the Conditional Apc Allele (A) Schematic diagram of exons 14 and 15 of the mouse Apc gene, the targeting vector, and the resulting conditional allele with 2 LoxP sites sandwiching the exon 14. The PGK-neomycin cassette was inserted within intron 14 by recombineering technique. This cassette is sandwiched by 2 FRT sites that could be removed by crossing to FLPe-expressing mice. Positions of PCR primers used for genotyping PCR (F2, R2, R4) and RT-PCR (F546 and R721) are indicated. Positions of probe used for Southern blot analysis with NdeI sites are also shown. Upon Cre-mediated recombination, exon 14 is removed and leads to truncated Apc protein, of which the first 580 aa correspond to the normal. (B) Southern blot analysis of NdeI-digested genomic tail DNA isolated from F1 mice of various Apc mouse lines (ApcCKON, ApcΔ580), hybridized to a 600-bp probe. Tail genomic DNA from ApcCKON F1 mice derived from a modified ES clone showed a 12-kb band for the ApcCKON allele and a 10-kb band for the wild-type allele, whereas genomic DNA from the ApcΔ580 mouse was heterozygous for the ApcΔ580 allele (9.2-kb band). (C) Kaplan-Meier survival plot of ApcCKO/+ mice (thin solid line, n = 39), ApcCKO/CKO mice (thin dotted line, n = 57), ApcΔ580/+ mice (solid line, n = 51), and wild-type littermates (broken line, n = 21). Heterozygosity of the ApcΔ580 allele led to a significantly shortened survival (p < 0.0001), whereas those of heterozygous and homozygous ApcCKO mice had no significant difference to that of wild-type littermates. Southern blot analysis of tail DNA from F1 offspring of both ApcCKON and ApcΔ580 lines confirmed the germline transmission of modified Apc allele (Figure 1B). Mice that are heterozygous for ApcΔ580 mutation are viable but have a significantly reduced lifespan (Figure 1C). These results suggested that deletion of exon 14 indeed results in either loss or abnormal function of the Apc gene product. ApcΔ580/+ mice have median survival of 5 mo of age (Figure 1C), with progressive signs of rectal bleeding and anemia. Similar to the results reported with an independently generated ApcΔ580/+ conditional mouse strain [14], ApcΔ580/+ mice had more than 100 (120 ± 37, n = 11) intestinal tumors at the time of their death (Figure S1). Inactivation of wild-type Apc is an important prerequisite for tumor development. We analyzed 30 intestinal tumors from ApcΔ580/+ mice by in vitro transcription and translation assay, but none of them showed truncated Apc products (unpublished data), indicating that the most likely mechanism of wild-type Apc inactivation is by allelic loss. The mutant allele had to be maintained and transmitted through male mice, as ApcΔ580/+ females were frequently not healthy enough to successfully nurse their own pups because of their tumor burden. ApcCKO/+ mice were intercrossed to generate ApcCKO/CKO offspring. Approximately one-quarter of the offspring (17 of 81) were homozygous for the ApcCKO allele. These mice as well as heterozygous mice for ApcCKO allele are normal, showing no differences in their survival to the wild-type littermates (Figure 1C). We tested whether our ApcCKO allele can compliment the wild-type allele by crossing the ApcCKO/CKO female with ApcΔ580/+ male mouse. The resultant ApcCKO/Δ580 offspring were viable and born in the Mendelian ratio, suggesting that the presence of loxP sites in introns flanking exon 14 have no adverse effect on the function of the Apc gene. K14-Driven Loss of Apc Results in Severe Growth Retardation and Early Lethality To introduce the mutation of Apc into cells expressing K14, we crossed WW6 ES cell–derived [15] ApcCKO/+ mice with K14-cre recombinase mice in FVB background [16]. The K14-cre; ApcCKO/+ mice were normal in appearance and were fertile. K14-cre; ApcCKO/+ males were crossed to ApcCKO/CKO females to avoid the potential deleter effect in oocytes of K14-cre–positive females [17]. The mice were intercrossed thereafter for maintenance; hence, the mice used for analysis were in a mixed background of FVB, 129/S, and C57BL/6 in similar proportions, with minimal contribution of SJ. The K14 promoter is a commonly used epidermal cell promoter because of its expression by the mitotically active cells of the epidermis and its appendages in mature skin [18], but most notably it is active in embryonic ectoderm as early as the single layered ectodermal stage of embryonic day (E) 9.5 [19]. A restricted expression of K14 is also found in thymic epithelial cells (TECs) in the medulla of normal thymus [20]. We genotyped a total of 458 pups (8–10 d old) from 67 litters resulting from crosses between K14-cre; ApcCKO/+ and ApcCKO/CKO mice. The mutant mice of the genotype K14-cre; ApcCKO/CKO (hereafter, KA mutant) were born, but the observed frequency of KA mutants was much less than expected (78 of 458 [17.0%]; p < 0.0005 Chi-square analysis, Table 1). To assess the basis for the neonatal lethality of KA mutants, we monitored three litters from birth to weaning by measuring the body weight of each pup every day. A total of 25 pups were born from three litters, of which 7 (28%) were confirmed to be K14-cre; ApcCKO/CKO by genotyping, indicating that KA mutants were born in the expected Mendelian ratio. The KA mutant pups were nursed normally, and there was milk in their stomachs during the first 2 or 3 d after birth, but they failed to thrive (Figure 2). By postnatal day (P) 8–10, at the time of genotyping, many KA mutant pups were considerably smaller than their littermates (Figure 2B–2F) and some have died at or prior to this age. None of KA mutants survived to weaning age. Table 1 Genotype Distribution of Progeny from the Matings Figure 2 Postnatal Mortality and Stunted Growth in K14-cre; ApcCKO/CKO Mutant Mice Animals whose genotype is either heterozygous or homozygous for the wild-type Apc allele are referred to as normal (N); those whose genotype are K14-cre; ApcCKO/CKO and show the presence of K14-cre–recombined mutant Apc allele are called mutant (M). (A) Two P3 mutant mice, M1 and M2, and their normal littermates, showing size variation among mutants. (B) P8 mutant mouse (right) and a normal littermate. Note sparseness of hair coat and abnormal ears. (C–D) Vibrissae of whisker pads are short and oddly angled in a P12 mutant mouse (C), relative to control (D). Note the lack of incisors in the mutant. (E) A P17 mutant mouse (right) with its littermate. Its bare forehead, dorsal median line, and abnormal ears are evident. (F) Growth curve of mutants and normal littermates. Mutants exhibit stunted growth, which became more prominent as they aged, and weigh significantly less than littermates from P8 (p < 0.05). (G) Comparison of mutant and normal thymus from P3 mice. The mutant thymus (left) is dramatically smaller for its age compared to the normal littermate (right). The scale bar equals 1 mm. (H) Skeletal preparations of normal (left) and mutant (right), showing differences in development of both incisor (I) and molar (M) teeth. The ability of whole embryos to exclude blue dye was used to examine the epidermal barrier, normally acquired beginning at E16 and complete by E18.5 [21]. Analyses of E17.5–E18.5 KA mutants showed that they were able to exclude blue dye, indicating that the epidermal barrier was intact (Figure S2). At these embryonic ages, there were no differences in size between the mutants and their littermates, but the mutants showed a patch of “birthmark” or dark pigmentation on their foreheads and a dark median line that ran caudally from head to tail. Their external ears or pinnae were shriveled in appearance and pigmented compared to those of littermates. External characteristics of KA mutants that were evident at E18.5 persisted after birth and became more prominent as they grew (Figure 2A–2F). Growth of pelage hair was generally delayed in the mutants. At around P8, the KA mutants were hairless and had wrinkled skin while their phenotypically normal littermates had a smooth thin coat of hair (Figure 2B). At this age, two lower incisors start to erupt in normal littermates and these were absent in the KA mutants (Figure 2C and 2D). Animals also tended to be smaller and around P10–P12 displayed abnormally short and misshapen vibrissae and short, shaggy pelage hairs (Figure 2C and 2D). Development of thick ridges in their skin, particularly around the ears, eyelids, forehead, nose, and paws, became noticeable (Figure 2E). These regions looked scaly, and these animals hardly kept their eyes open. In contrast to the normal littermates that consistently increased their body weight with age, surviving KA mutants started to lose weight from P10 onwards; by P16–P17 they were all lethargic, and none of them survived to weaning (Figure 2E and 2F). At the time of autopsy all the mutants were toothless, without incisors or molars, and their stomachs were consistently small and had no solid food, unlike their age-matched littermates, suggesting that the observed weight loss could be the result of failure to ingest solid food (Figure 2F). Interestingly, changes in body weights and timing of hair growth varied considerably among mutant pups even if they were from the same litter, whereas those of phenotypically normal littermates tended to be similar. This difference was also reflected in the variation in timing of death in mutants: some mutant pups were born alive but died within a day or two, some survived close to the weaning age. This variability of the mutant phenotypes suggests possible variation in the timing and efficiency of cre-mediated Apc deletion. It is possible that the genetic background has a role to play in this variability. Gross examination of internal organs also showed that the mutants' thymi were consistently inconspicuous and were very small for their age, whereas those of their littermates were very prominent in size (Figure 2G). This difference was evident as early as P3. Quite frequently mutant thymi in P12–P17 mutant mice also contained black deposits within the tissue (unpublished data). Mutant mice were also examined for any skeletal abnormalities by preparing skeletal specimens of P16–P17 mice stained with Alizarin red. No differences between the normal and KA mutant mice in the mandibular bone can be detected, but the mutant mice lacked or had underdeveloped set of maxillary incisors and molars (Figure 2H). We detected no other major skeletal abnormalities. Genotype- and Tissue-Specific Expression of the Truncated Apc Transcripts To assess the molecular effects of the K14-cre–mediated recombination, we screened for the presence of deleted Apc (ApcΔ580) alleles. Genomic DNA was extracted from liver, thymus, and skin from all 4 possible genotypes: K14-cre; ApcCKO/CKO, K14-cre; ApcCKO/+, ApcCKO/CKO, and ApcCKO/+. Genotyping on genomic DNA from these tissues showed that the ApcΔ580 allele (500-bp product) was detected only from the skin and thymus of the K14-cre–positive mice. The presence of mutant Apc allele in the thymus of K14-cre; ApcCKO/+ mice was consistently much less than the DNA from the skin of the same animal or other tissues from the KA mutants. In addition, this product was not detected at all in either the liver of K14-cre–positive or in any of the K14-cre–negative mouse tissues samples, establishing that Cre-mediated recombination has taken place in the tissue-specific manner in the mice that inherited K14-cre (Figure 3A). Figure 3 Tissue-Specific Detection and Expression of Deleted Apc Alleles (A) Tissue-specific genotyping PCR. Only genomic DNA samples from the skin (S) and thymus (T), but not liver (L) of mice positive for K14-cre show the presence of deleted ApcΔ580 allele. (B) Genotype- and tissue-specific expression of the truncated Apc transcripts. A representative gel of RT-PCR using primers F546 and R721, showing that only RNA from the skin and thymus but not liver of mice positive for K14-cre have transcripts from both wild-type (528 bp) and deleted (313 bp) Apc alleles. Apc transcripts were also analyzed by RT-PCR with primers spanning exon 14 (Figure 1A) using total RNA isolated from the corresponding tissue samples. We detected the expected RT-PCR product (313 bp) from the truncated Apc (ApcΔ580) allele only in the tissues where Cre recombinase is known to be expressed in the K14-cre–positive mice. However, this product was not detected in either the K14-cre–negative mouse tissues samples or the liver of K14-cre–positive mice, and only the product from the wild-type allele (528 bp) was detected from these RNA samples, further confirming that Cre-mediated recombination has taken place in the tissue- and genotype-specific manner (Figure 3B). K14-cre–Driven Apc Loss Induced Aberrant Hair Follicles throughout the Epidermis To understand the basis for delayed and abnormal hair development in the KA mutants, we conducted a histological and immunohistochemical examination (Figure 4). The hair follicle is an epidermal appendage that consists of an upper permanent portion, and a lower cycling portion that produces the hair [22,23]. The outer root sheath (ORS) is contiguous with and biochemically similar to the basal layer of the epidermis. The inner layers of the hair follicle include three concentric layers of inner root sheath and three concentric layers of hair-producing cells. At the base of the hair follicle is the germinative hair follicle bulb, which contains rapidly proliferating “matrix” cells that differentiate to populate all of the layers of the inner root sheath and the hair shaft itself [22]. During the anagen phase of the hair cycle (until P15), hair follicles of phenotypically normal mice grew deeply into the subcutaneous fat and were uniformly spaced and aligned in parallel arrays at a specific angle relative to the skin surface (Figure 4A). In contrast, KA mutant follicles were irregularly spaced and often seen as disoriented and clamped invaginations at P3 that became even more remarkable at P12 when the mutant mice were covered by fur coat (Figure 4F). Bulbs were often bent in addition to being irregularly angled to one another and their sizes and locations were often variable. Clusters of multiple invaginations or dysplastic follicular structures were frequently observed throughout the epidermis, whereas other regions showed gaps with no follicles. Serial sectioning indicated that some of the hair follicles in the P12 mutant skin were not properly formed or shorter than normal. Taken together, these features could account for the apparently delayed, followed by outgrowth, of the short and shaggy-looking fur coat of these mutant mice. Figure 4 Histological and Immunochemical Examination of P12 Skin and Teeth (A–E) P12 normal skin. (F–J) P12 mutant skin. (K–N) P12 normal oral cavity. (O–R) P12 mutant oral cavity. Stained with H&E for histology (A, F, K–L, O–P), Ki67 (B, G), β-catenin (C, H, M, Q), K14 (D, I, N, R), and K6 (E, J). Aberrant follicular morphogenesis, characterized by formation of irregularly spaced, nonpolarized hair follicles, in mutant skin is evident. Despite the abnormal histology, proliferation seems to be confined to hair bulb-like structures (arrows in [G], inset [G′] at higher magnification), but in mutant skin (arrows in [H], inset [H′] at higher magnification) and oral cavity (arrows in insets [Q′] at higher magnification) elevated cytosolic localization of β-catenin is detected in some cells. Scale bars: 50 μm for (A–F), (H–J); 250 μm for (K) and (O); 100 μm for (G), (L–N), (P–R); 20 μm for (Q′). Apc is a regulator of β-catenin that is important for Wnt signaling. We examined the patterns of expression of β-catenin in the affected tissues. In the normal skin, β-catenin, a member of the adherens junction complex, was found in the ORS of hair follicles and basal layer of epidermis, where K14 expression is also observed (Figure 4C and 4D), whereas the expression of K1, involucrin, and loricrin (markers for spinous and granular layers of epidermis) was only observed in the nonbasal epidermis (unpublished data). The patterns of expression of K14, K1, involucrin, and loricrin, in skin from mutant and normal littermate mice at P3–P17, showed no significant differences in the terminal differentiation (Figure 4A–4D, 4F–4I). Similarly, the pattern of expression of K6, which is normally only expressed in the suprabasal or inner layer of the ORS of the hair follicle but not in the epidermis (Figure 4E), did not change. Due to the abnormal and disorganized structure of hair follicles themselves, K6 localization highlighted the histological abnormality (Figure 4J). Yet as in the normal skin, K6 was principally seen only in the suprabasal layer of the ORS that did not colocalize with the basal markers, K14 or K5 (Figure 4I and 4J). In normal skin, proliferating cells were detected in either the basal layer of epidermis or in germinative hair follicle bulbs at the base (Figure 4B). In the mutant skin, either BrdU incorporation or Ki67 expression was observed not only in cells in bulbs at the base of the hair follicle but also in bulb-like structures that were budding out from the ORS of the existing hair follicles (Figure 4G and 4G′). Each budding tip was becoming like a hair follicle bulb containing proliferating cells. Hence, despite the abnormal histology in the mutant skin, proliferation seems to be confined to bulb-like structures as in the normal skin (Figure 4G and 4G′). The exact locations of hair follicle bulbs were not as easy to define for some mutant follicles due to their disorganized structures. Interestingly, in the mutant skin, in addition to diffuse membrane-bound localization as in the normal skin, cells with strong cytosolic β-catenin localization were also observed frequently (Figure 4H and 4H′). These elevated β-catenin–expressing cells were usually surrounded by proliferating cells, forming bulb-like structures. Comparison of immunochemically stained serial sections showed that these intense cytosolic β-catenin stainings were usually found in either K14-positive K1-negative basal epidermis or K14-positive K6-negative basal ORS cells, and are surrounded by proliferating cells. To determine the initiation of hair follicle morphogenesis in these mutants, we examined the expression pattern of Sonic hedgehog (Shh), a factor expressed in hair bulbs in embryonic skin (Figure 5). The aberrant hair follicle morphogenesis is evident as early as E14.5 in mutant embryonic skin, by multiple apolarized expression of Shh throughout the epidermis (Figure 5B), whereas that of control embryos was well polarized and regularly spaced (Figure 5A). With development, control mouse hair follicles invaginate downward in a polarized manner (Figure 5C), whereas those of mutant embryos were completely irregular and apolarized (Figure 5D). It was also noted that the size of each “budding” follicle, as detected by Shh expression, was variable (Figure 5D). The intensity of Shh staining was generally stronger in mutant skin than in the normal skin. The aberrant initiation of multiple hair placodes during early hair follicle morphogenesis was also evident by the whole-mount in situ hybridization (ISH) of E15.5 mutant embryos for β-catenin (Figure 5F and 5F′). The expression pattern of β-catenin in embryos clearly demonstrated the formation of regular arrays of hair placodes in the normal embryonic skin (Figure 5E and 5E′), but such regular patterning was lost, and often tightly clustered abnormal hair placodes were initiated in mutant embryonic skin (Figure 5F′). Aberrant hair placodes were also evident throughout the skin surface of limbs in E15.5 mutants (Figure 5F), whereas those of the control embryos had not yet formed (Figure 5E). Most interestingly, in the mutant footpads, where hair placodes do not normally form (Figure 5G), we also found ectopic irregularly sized and spaced hair placodes, indicating that the footpads still have the potential to form hair placodes in the absence of the Apc gene (Figure 5H). Figure 5 Expression of Shh and β-catenin Transcripts in Normal (ApcCKO/CKO) and Mutant (K14-cre; ApcCKO/CKO) Embryonic Skin (A–D) Section ISH with Shh probe in E14.5 normal (A), E14.5 mutant (B), E16.5 normal (C), and E16.5 mutant (D) skin. Broken lines indicate the interface between epithelium and mesenchyme. Scale bars: 50 μm. Whole mount in situ detection of β-catenin in E15.5 normal (E, G), mutant (F, H) embryos. Aberrant initiation of multiple hair placodes is evident at E14.5. Loss of K14-driven Apc loss caused aberrant pattern formation (F′) and formed ectopic hair placodes in normally hairless foot pads (H, arrows) which are absent in normal (G). These results collectively suggest that the terminal differentiation does take place normally in the mutant skin, but initiation of embryonic hair follicle morphogenesis is severely disrupted, accompanied by a continuous ectopic hair follicle morphogenesis in postnatal mutant skin. Effects of K14-cre–Driven Loss of Apc in Other Epidermal Appendages Similar to the biology of hair follicles, K14-cre–driven loss of Apc also affected the development of other epidermal appendages that depend on epithelial–mesenchymal interactions for their formation. The most striking of these was dental dysplasia (Figure 4K–4R). Tooth development is normally initiated between E11 and E12 by invagination of ectodermally derived oral epithelium into the underlying cranial neural crest–derived mesenchyme, generating a tooth germ. Despite the grossly toothless phenotype of KA mutants, histological analysis of their oral cavities revealed the formation of multiple tooth buds at each location. These aberrant teeth obviously failed to grow out during the dietary transition from milk to solid food. Analogous to the expression patterns of K14 and β-catenin in the normal skin, diffuse membrane-bound expression of β-catenin was detected in K14-expressing oral epithelium and ameloblasts of normal mice. In mutants, some of the K14-expressing cells also showed strong cytosolic/nuclear β-catenin staining, as observed in the mutant skin (Figure 4Q, 4Q′, and 4R). Initiation of ectopic tooth buds in the mutant mice was evident at E15.5 by extra dots of Shh expression adjacent to the primary teeth (data not shown). Loss of Apc also leads to hyperplasia in squamous epithelia of cornea, oral, salivary, and Hardarian glands (unpublished data). Squamous metaplasia to hair follicle–like structures, ectopic hair follicle morphogenesis was also observed in these epithelia. K14-cre–Driven Apc Loss Results in Hypoplastic/Athymic Mice Thymus is an organ that is also known to have K14 expression [16]. It represents the primary lymphoid organ for thymocyte development and selection. Distinct population of TECs of cortex and medulla mediates both of these critical functions. Cortical and medullary TEC subsets are characterized by differential expression of four keratin species: K8, K18, K5, and K14. The normal thymus is a lobulated lymphoid organ, each lobule clearly showing the two distinct TEC compartments, an outer cortex and an inner medulla (Figure 6). There were no major differences in the histology of thymus between the ages P3 to P17 in phenotypically normal littermates. As shown in the H&E staining of thymus, the cortex was formed of dense lymphoid tissue that lacks nodules (Figure 6A). Since the stroma of the medulla is less heavily infiltrated with lymphocytes than the cortex, the medulla stained more lightly than the cortex. In normal mice, the thymus retains its size until the young adult age and regresses thereafter by atrophy. In the normal young mice we examined (P3–P17), it is evident that thymocytes were mitotically active in the cortex as determined by BrdU immunostaining (Figure 6B). Immunohistochemistry of normal thymus from P3 to P17 mice showed a similar staining pattern for K14 in that its expression was restricted to a small population of TECs in the inner medullary region and in the keratinocytes in Hassall's corpuscles (Figure 6D). Diffuse cytoplasmic staining for β-catenin was also detected in the medullary epithelial cells (Figure 6C). In contrast to K14 expression, diffuse staining for K8 was observed in epithelial cells both in the medulla and cortex (Figure S3). K1 staining was not detected in young mice at P3 but in older mice it was detected in differentiated keratinocytes in some of Hassall's corpuscles (Figure S3). Figure 6 Histological and Immunochemical Examination of Thymus (A–D) P3 normal thymus. (E–G) Mild P3 mutant thymus. (H–K) Severe P3 mutant thymus. (L–O) P13 mutant thymus. Stained with H&E for histology (A, E, H, L), BrdU (B, I, M), β-catenin (C, F, J, N), and K14 (D, G, K, O). (B) Actively dividing thymocytes are visible at the superficial edge of cortex of normal P3 thymus. Note the progression of histological abnormalities in the mutant thymus from mild P3, severe P3 to P13 (A, E, H, L). Scale bars, 20 μm. The histological abnormalities of thymus were evident as early as P3 in KA mutants (Figure 6E and 6H). The thymus was made of two lobules as in the normal mice but the mutant thymus was significantly smaller in size than that of the age-matched controls (Figure 2G). Interestingly, variations in the phenotypic severity of the mutant pups at P3 were prominently reflected in the extent of histological abnormalities of thymus. A P3 KA mutant pup that showed milder phenotype with a comparable body weight to its normal littermates (Figure 2A, M2) showed milder thymus abnormalities (Figure 6E) compared to its more severe mutant littermate (Figure 2A, M1; Figure 6H). The milder P3 mutant thymus was already much smaller in size compared to those of normal littermates (data not shown) but two epithelial compartments of thymus were histologically still distinguishable, with colonization of thymocytes evident in the cortex. However, there were small populations of lightly stained cells by H&E extending from the edge of the outer cortex towards inner medulla (Figure 6E), and these cells showed intense nuclear β-catenin staining whereas the rest of the medullary cells showed diffuse β-catenin staining pattern similar to that of the control (Figure 6F). Localization of K14 was limited to a few cells in the medulla and some overlapped with K8 localization (Figure 6G). In the other P3 mutant thymus the distinct thymic epithelial compartments have been lost completely, and only a few lymphocytes were remaining at the edges and some in the middle (Figure 6H). Proliferative activities were no longer observed in thymocytes as prominently as in the normal thymus, but the epithelial cells seemed to be forming concentric structures (Figure 6I). Unlike in the normal or mild mutant thymi, the severe P3 mutant thymus showed extensive K14 expression that overlapped with K8 expression (Figure 6K). These cells were more like basal cells of the skin than TECs and were adjacent to the most immature looking cells that were showing strong nuclear and cytoplasmic β-catenin staining (Figure 6J). The nuclear staining of β-catenin was not observed in the normal age-matched thymus (Figure 6C). Most notably, the K14 and β-catenin staining patterns were mutually exclusive (Figure 6J and 6K). At P10–P13, the mutant thymus consisted of numerous enlarged Hassall's corpuscle–like structures, made of arrays of K14- and K8-expressing keratinizing epithelial cells surrounding large keratin deposits (Figure 6L and 6O). There were numerous neutrophils and macrophages infiltrating the thymus in response to these keratins; hence, these structures could be called pyogranuloma. Varying degrees of differentiation-specific markers depending on the age of mice, in this case K1 and involucrin that are normally present only in Hassall's corpuscles, were also detected in mutant thymi (Figure S3). In these mice no thymocytes were detectable. BrdU incorporation was only observed in very few keratinizing epithelial cells, looking somewhat similar to the pattern of mature skin (Figure 6M). The diffuse expression of β-catenin was also present in these epithelial cells, and at this age fewer cells were positive for nuclear β-catenin staining (Figure 6N). As in the younger mutant mice, however, nuclear localization of β-catenin was only observed in K14-negative cells that looked like undifferentiated basal cells. In older P17 mice, the histopathology and keratin expression pattern of the mutant thymus was similar to that of P13 except for the fact that β-catenin expression became increasingly diffuse and appeared to colocalize with K8/K14 expression (data not shown). This coincided with fewer immature cells in the older mutant thymus. Collectively, these results suggest that loss of Apc and consequent stabilization of β-catenin in K14-expressing TECs lead to their aberrant proliferation and differentiation to keratinocytes, causing massive squamous metaplasia, rather than to form either medullary or cortical TECs. Loss of proper TEC compartments consequently resulted in loss of thymocytes for maturation and the mice to be “athymic.” Discussion Apc
T19065 37370-37380 VBN denotes implicated
T19066 37367-37369 VBZ denotes is
T19067 37381-37383 IN denotes in
T19068 37384-37387 DT denotes the
T19069 37402-37409 NN denotes pathway
T19070 37388-37391 NN denotes Wnt
T19071 37392-37401 NN denotes signaling
T19072 37410-37414 WDT denotes that
T19073 37418-37426 VBN denotes involved
T19074 37415-37417 VBZ denotes is
T19075 37427-37431 CC denotes both
T19076 37432-37434 IN denotes in
T19077 37435-37446 NN denotes development
T19078 37447-37450 CC denotes and
T19079 37451-37464 NN denotes tumorigenesis
T19080 37464-37465 . denotes .
T19081 37465-37683 sentence denotes Human germline mutations in APC cause FAP [4,5], which is characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer in the third and fourth decades of life.
T19082 37466-37471 JJ denotes Human
T19083 37481-37490 NNS denotes mutations
T19084 37472-37480 NN denotes germline
T19085 37498-37503 VBP denotes cause
T19086 37491-37493 IN denotes in
T19087 37494-37497 NN denotes APC
T19088 37504-37507 NN denotes FAP
T19089 37508-37509 -LRB- denotes [
T19090 37511-37512 CD denotes 5
T19091 37509-37510 CD denotes 4
T19092 37510-37511 , denotes ,
T19093 37512-37513 -RRB- denotes ]
T19094 37513-37515 , denotes ,
T19095 37515-37520 WDT denotes which
T19096 37524-37537 VBN denotes characterized
T19097 37521-37523 VBZ denotes is
T19098 37538-37540 IN denotes by
T19099 37541-37549 NNS denotes hundreds
T19100 37550-37552 IN denotes of
T19101 37553-37564 JJ denotes adenomatous
T19102 37576-37582 NNS denotes polyps
T19103 37565-37575 JJ denotes colorectal
T19104 37582-37584 , denotes ,
T19105 37584-37588 IN denotes with
T19106 37589-37591 DT denotes an
T19107 37610-37621 NN denotes progression
T19108 37592-37598 RB denotes almost
T19109 37599-37609 JJ denotes inevitable
T19110 37622-37624 IN denotes to
T19111 37625-37635 JJ denotes colorectal
T19112 37636-37642 NN denotes cancer
T19113 37643-37645 IN denotes in
T19114 37646-37649 DT denotes the
T19115 37667-37674 NNS denotes decades
T19116 37650-37655 JJ denotes third
T19117 37656-37659 CC denotes and
T19118 37660-37666 JJ denotes fourth
T19119 37675-37677 IN denotes of
T19120 37678-37682 NN denotes life
T19121 37682-37683 . denotes .
T19122 37683-37775 sentence denotes The phenotypical features of FAP and its variant, Gardner's syndrome, can be very variable.
T19123 37684-37687 DT denotes The
T19124 37701-37709 NNS denotes features
T19125 37688-37700 JJ denotes phenotypical
T19126 37758-37760 VB denotes be
T19127 37710-37712 IN denotes of
T19128 37713-37716 NN denotes FAP
T19129 37717-37720 CC denotes and
T19130 37721-37724 PRP$ denotes its
T19131 37725-37732 NN denotes variant
T19132 37732-37734 , denotes ,
T19133 37734-37741 NNP denotes Gardner
T19134 37744-37752 NN denotes syndrome
T19135 37741-37743 POS denotes 's
T19136 37752-37754 , denotes ,
T19137 37754-37757 MD denotes can
T19138 37761-37765 RB denotes very
T19139 37766-37774 JJ denotes variable
T19140 37774-37775 . denotes .
T19141 37775-38062 sentence denotes As well as colorectal polyps, these individuals can develop extracolonic symptoms, among which are upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, disorders of the maxillary and skeletal bones, and dental abnormalities [6].
T19142 37776-37778 RB denotes As
T19143 37784-37786 IN denotes as
T19144 37779-37783 RB denotes well
T19145 37798-37804 NNS denotes polyps
T19146 37787-37797 JJ denotes colorectal
T19147 37828-37835 VB denotes develop
T19148 37804-37806 , denotes ,
T19149 37806-37811 DT denotes these
T19150 37812-37823 NNS denotes individuals
T19151 37824-37827 MD denotes can
T19152 37836-37848 JJ denotes extracolonic
T19153 37849-37857 NNS denotes symptoms
T19154 37857-37859 , denotes ,
T19155 37859-37864 IN denotes among
T19156 37871-37874 VBP denotes are
T19157 37865-37870 WDT denotes which
T19158 37875-37880 JJ denotes upper
T19159 37898-37903 NN denotes tract
T19160 37881-37897 JJ denotes gastrointestinal
T19161 37904-37910 NNS denotes polyps
T19162 37910-37912 , denotes ,
T19163 37912-37922 JJ denotes congenital
T19164 37923-37934 NN denotes hypertrophy
T19165 37935-37937 IN denotes of
T19166 37938-37941 DT denotes the
T19167 37958-37968 NN denotes epithelium
T19168 37942-37949 JJ denotes retinal
T19169 37950-37957 NN denotes pigment
T19170 37968-37970 , denotes ,
T19171 37970-37977 JJ denotes desmoid
T19172 37978-37984 NNS denotes tumors
T19173 37984-37986 , denotes ,
T19174 37986-37995 NNS denotes disorders
T19175 37996-37998 IN denotes of
T19176 37999-38002 DT denotes the
T19177 38026-38031 NNS denotes bones
T19178 38003-38012 JJ denotes maxillary
T19179 38013-38016 CC denotes and
T19180 38017-38025 JJ denotes skeletal
T19181 38031-38033 , denotes ,
T19182 38033-38036 CC denotes and
T19183 38037-38043 JJ denotes dental
T19184 38044-38057 NNS denotes abnormalities
T19185 38058-38059 -LRB- denotes [
T19186 38059-38060 CD denotes 6
T19187 38060-38061 -RRB- denotes ]
T19188 38061-38062 . denotes .
T19189 38062-38216 sentence denotes While the heterozygous knockout mice for Apc develop adenomatous polyps predominantly in small intestine, the homozygous embryos die before gastrulation.
T19190 38063-38068 IN denotes While
T19191 38108-38115 VBP denotes develop
T19192 38069-38072 DT denotes the
T19193 38095-38099 NNS denotes mice
T19194 38073-38085 JJ denotes heterozygous
T19195 38086-38094 NN denotes knockout
T19196 38100-38103 IN denotes for
T19197 38104-38107 NN denotes Apc
T19198 38192-38195 VBP denotes die
T19199 38116-38127 JJ denotes adenomatous
T19200 38128-38134 NNS denotes polyps
T19201 38135-38148 RB denotes predominantly
T19202 38149-38151 IN denotes in
T19203 38152-38157 JJ denotes small
T19204 38158-38167 NN denotes intestine
T19205 38167-38169 , denotes ,
T19206 38169-38172 DT denotes the
T19207 38184-38191 NNS denotes embryos
T19208 38173-38183 JJ denotes homozygous
T19209 38196-38202 IN denotes before
T19210 38203-38215 NN denotes gastrulation
T19211 38215-38216 . denotes .
T19212 38216-38542 sentence denotes To gain more insights into the effects of Apc loss in tissues other than gastrointestinal tract during life of animals and to circumvent the embryonic lethality associated with Apc nullizygosity, we created a mouse strain carrying a conditional allele of Apc (ApcCKO) in which exon 14 of the Apc is flanked by loxP sequences.
T19213 38217-38219 TO denotes To
T19214 38220-38224 VB denotes gain
T19215 38416-38423 VBD denotes created
T19216 38225-38229 JJR denotes more
T19217 38230-38238 NNS denotes insights
T19218 38239-38243 IN denotes into
T19219 38244-38247 DT denotes the
T19220 38248-38255 NNS denotes effects
T19221 38256-38258 IN denotes of
T19222 38259-38262 NN denotes Apc
T19223 38263-38267 NN denotes loss
T19224 38268-38270 IN denotes in
T19225 38271-38278 NNS denotes tissues
T19226 38279-38284 JJ denotes other
T19227 38285-38289 IN denotes than
T19228 38290-38306 JJ denotes gastrointestinal
T19229 38307-38312 NN denotes tract
T19230 38313-38319 IN denotes during
T19231 38320-38324 NN denotes life
T19232 38325-38327 IN denotes of
T19233 38328-38335 NNS denotes animals
T19234 38336-38339 CC denotes and
T19235 38340-38342 TO denotes to
T19236 38343-38353 VB denotes circumvent
T19237 38354-38357 DT denotes the
T19238 38368-38377 NN denotes lethality
T19239 38358-38367 JJ denotes embryonic
T19240 38378-38388 VBN denotes associated
T19241 38389-38393 IN denotes with
T19242 38394-38397 NN denotes Apc
T19243 38398-38411 NN denotes nullizygosity
T19244 38411-38413 , denotes ,
T19245 38413-38415 PRP denotes we
T19246 38424-38425 DT denotes a
T19247 38432-38438 NN denotes strain
T19248 38426-38431 NN denotes mouse
T19249 38439-38447 VBG denotes carrying
T19250 38448-38449 DT denotes a
T19251 38462-38468 NN denotes allele
T19252 38450-38461 JJ denotes conditional
T19253 38469-38471 IN denotes of
T19254 38472-38475 NN denotes Apc
T19255 38476-38477 -LRB- denotes (
T19256 38477-38483 NN denotes ApcCKO
T19257 38483-38484 -RRB- denotes )
T19258 38485-38487 IN denotes in
T19259 38516-38523 VBN denotes flanked
T19260 38488-38493 WDT denotes which
T19261 38494-38498 NN denotes exon
T19262 38499-38501 CD denotes 14
T19263 38502-38504 IN denotes of
T19264 38505-38508 DT denotes the
T19265 38509-38512 NN denotes Apc
T19266 38513-38515 VBZ denotes is
T19267 38524-38526 IN denotes by
T19268 38527-38531 NN denotes loxP
T19269 38532-38541 NNS denotes sequences
T19270 38541-38542 . denotes .
T19271 38542-38723 sentence denotes The homozygous mice for the conditional allele are viable and indistinguishable to the normal mice, allowing us to study the roles of Apc in a tissue- and temporal-specific manner.
T19272 38543-38546 DT denotes The
T19273 38558-38562 NNS denotes mice
T19274 38547-38557 JJ denotes homozygous
T19275 38590-38593 VBP denotes are
T19276 38563-38566 IN denotes for
T19277 38567-38570 DT denotes the
T19278 38583-38589 NN denotes allele
T19279 38571-38582 JJ denotes conditional
T19280 38594-38600 JJ denotes viable
T19281 38601-38604 CC denotes and
T19282 38605-38622 JJ denotes indistinguishable
T19283 38623-38625 IN denotes to
T19284 38626-38629 DT denotes the
T19285 38637-38641 NNS denotes mice
T19286 38630-38636 JJ denotes normal
T19287 38641-38643 , denotes ,
T19288 38643-38651 VBG denotes allowing
T19289 38652-38654 PRP denotes us
T19290 38658-38663 VB denotes study
T19291 38655-38657 TO denotes to
T19292 38664-38667 DT denotes the
T19293 38668-38673 NNS denotes roles
T19294 38674-38676 IN denotes of
T19295 38677-38680 NN denotes Apc
T19296 38681-38683 IN denotes in
T19297 38684-38685 DT denotes a
T19298 38716-38722 NN denotes manner
T19299 38686-38692 NN denotes tissue
T19300 38707-38715 JJ denotes specific
T19301 38692-38693 HYPH denotes -
T19302 38694-38697 CC denotes and
T19303 38698-38706 JJ denotes temporal
T19304 38706-38707 HYPH denotes -
T19305 38722-38723 . denotes .
T19306 38724-38911 sentence denotes To assess the phenotypic consequences of inactivation of the Apc gene in cells that express K14, we created mice that are homozygous for the ApcCKO allele and contain a K14-cre transgene.
T19307 38724-38726 TO denotes To
T19308 38727-38733 VB denotes assess
T19309 38824-38831 VBD denotes created
T19310 38734-38737 DT denotes the
T19311 38749-38761 NNS denotes consequences
T19312 38738-38748 JJ denotes phenotypic
T19313 38762-38764 IN denotes of
T19314 38765-38777 NN denotes inactivation
T19315 38778-38780 IN denotes of
T19316 38781-38784 DT denotes the
T19317 38789-38793 NN denotes gene
T19318 38785-38788 NN denotes Apc
T19319 38794-38796 IN denotes in
T19320 38797-38802 NNS denotes cells
T19321 38803-38807 WDT denotes that
T19322 38808-38815 VBP denotes express
T19323 38816-38819 NN denotes K14
T19324 38819-38821 , denotes ,
T19325 38821-38823 PRP denotes we
T19326 38832-38836 NNS denotes mice
T19327 38837-38841 WDT denotes that
T19328 38842-38845 VBP denotes are
T19329 38846-38856 JJ denotes homozygous
T19330 38857-38860 IN denotes for
T19331 38861-38864 DT denotes the
T19332 38872-38878 NN denotes allele
T19333 38865-38871 NN denotes ApcCKO
T19334 38879-38882 CC denotes and
T19335 38883-38890 VBP denotes contain
T19336 38891-38892 DT denotes a
T19337 38901-38910 NN denotes transgene
T19338 38893-38896 NN denotes K14
T19339 38897-38900 NN denotes cre
T19340 38896-38897 HYPH denotes -
T19341 38910-38911 . denotes .
T19342 38911-38964 sentence denotes These mice failed to thrive and died before weaning.
T19343 38912-38917 DT denotes These
T19344 38918-38922 NNS denotes mice
T19345 38923-38929 VBD denotes failed
T19346 38930-38932 TO denotes to
T19347 38933-38939 VB denotes thrive
T19348 38940-38943 CC denotes and
T19349 38944-38948 VBD denotes died
T19350 38949-38955 IN denotes before
T19351 38956-38963 VBG denotes weaning
T19352 38963-38964 . denotes .
T19353 38964-39020 sentence denotes They also exhibited hair, tooth, and thymus phenotypes.
T19354 38965-38969 PRP denotes They
T19355 38975-38984 VBD denotes exhibited
T19356 38970-38974 RB denotes also
T19357 38985-38989 NN denotes hair
T19358 39009-39019 NNS denotes phenotypes
T19359 38989-38991 , denotes ,
T19360 38991-38996 NN denotes tooth
T19361 38996-38998 , denotes ,
T19362 38998-39001 CC denotes and
T19363 39002-39008 NN denotes thymus
T19364 39019-39020 . denotes .
T22183 39022-39025 NN denotes Apc
T22184 39044-39057 NN denotes Morphogenesis
T22185 39026-39029 CC denotes and
T22186 39030-39034 NN denotes Hair
T22187 39035-39043 NN denotes Follicle
T22188 39057-39330 sentence denotes Current models of hair follicle development suggest that the establishment of a regular array of placodes in the surface epithelium in response to the first dermal message is achieved through the competing activities of molecules that promote or repress placode fate [24].
T22189 39058-39065 JJ denotes Current
T22190 39066-39072 NNS denotes models
T22191 39102-39109 VBP denotes suggest
T22192 39073-39075 IN denotes of
T22193 39076-39080 NN denotes hair
T22194 39081-39089 NN denotes follicle
T22195 39090-39101 NN denotes development
T22196 39110-39114 IN denotes that
T22197 39233-39241 VBN denotes achieved
T22198 39115-39118 DT denotes the
T22199 39119-39132 NN denotes establishment
T22200 39133-39135 IN denotes of
T22201 39136-39137 DT denotes a
T22202 39146-39151 NN denotes array
T22203 39138-39145 JJ denotes regular
T22204 39152-39154 IN denotes of
T22205 39155-39163 NNS denotes placodes
T22206 39164-39166 IN denotes in
T22207 39167-39170 DT denotes the
T22208 39179-39189 NN denotes epithelium
T22209 39171-39178 NN denotes surface
T22210 39190-39192 IN denotes in
T22211 39193-39201 NN denotes response
T22212 39202-39204 IN denotes to
T22213 39205-39208 DT denotes the
T22214 39222-39229 NN denotes message
T22215 39209-39214 JJ denotes first
T22216 39215-39221 JJ denotes dermal
T22217 39230-39232 VBZ denotes is
T22218 39242-39249 IN denotes through
T22219 39250-39253 DT denotes the
T22220 39264-39274 NNS denotes activities
T22221 39254-39263 VBG denotes competing
T22222 39275-39277 IN denotes of
T22223 39278-39287 NNS denotes molecules
T22224 39288-39292 WDT denotes that
T22225 39293-39300 VBP denotes promote
T22226 39301-39303 CC denotes or
T22227 39304-39311 VBP denotes repress
T22228 39312-39319 NN denotes placode
T22229 39320-39324 NN denotes fate
T22230 39325-39326 -LRB- denotes [
T22231 39326-39328 CD denotes 24
T22232 39328-39329 -RRB- denotes ]
T22233 39329-39330 . denotes .
T22234 39330-39477 sentence denotes There is accumulating evidence that activation of the Wnt signaling pathway in the dermis may be involved in establishing the first dermal signal.
T22235 39331-39336 EX denotes There
T22236 39337-39339 VBZ denotes is
T22237 39340-39352 VBG denotes accumulating
T22238 39353-39361 NN denotes evidence
T22239 39362-39366 IN denotes that
T22240 39428-39436 VBN denotes involved
T22241 39367-39377 NN denotes activation
T22242 39378-39380 IN denotes of
T22243 39381-39384 DT denotes the
T22244 39399-39406 NN denotes pathway
T22245 39385-39388 NN denotes Wnt
T22246 39389-39398 NN denotes signaling
T22247 39407-39409 IN denotes in
T22248 39410-39413 DT denotes the
T22249 39414-39420 NN denotes dermis
T22250 39421-39424 MD denotes may
T22251 39425-39427 VB denotes be
T22252 39437-39439 IN denotes in
T22253 39440-39452 VBG denotes establishing
T22254 39453-39456 DT denotes the
T22255 39470-39476 NN denotes signal
T22256 39457-39462 JJ denotes first
T22257 39463-39469 JJ denotes dermal
T22258 39476-39477 . denotes .
T22259 39477-39715 sentence denotes Experimental activation of epithelial β-catenin signaling (by expression of N-terminal–truncated, constitutively stabilized forms of β-catenin or ectopic expression of Lef1) induces ectopic follicles in both mouse and chick skin [25–27].
T22260 39478-39490 JJ denotes Experimental
T22261 39491-39501 NN denotes activation
T22262 39652-39659 VBZ denotes induces
T22263 39502-39504 IN denotes of
T22264 39505-39515 JJ denotes epithelial
T22265 39526-39535 NN denotes signaling
T22266 39516-39517 NN denotes β
T22267 39518-39525 NN denotes catenin
T22268 39517-39518 HYPH denotes -
T22269 39536-39537 -LRB- denotes (
T22270 39537-39539 IN denotes by
T22271 39540-39550 NN denotes expression
T22272 39551-39553 IN denotes of
T22273 39554-39555 NN denotes N
T22274 39556-39564 NN denotes terminal
T22275 39555-39556 HYPH denotes -
T22276 39565-39574 JJ denotes truncated
T22277 39564-39565 HYPH denotes
T22278 39602-39607 NNS denotes forms
T22279 39574-39576 , denotes ,
T22280 39576-39590 RB denotes constitutively
T22281 39591-39601 VBN denotes stabilized
T22282 39608-39610 IN denotes of
T22283 39611-39612 NN denotes β
T22284 39613-39620 NN denotes catenin
T22285 39612-39613 HYPH denotes -
T22286 39621-39623 CC denotes or
T22287 39624-39631 JJ denotes ectopic
T22288 39632-39642 NN denotes expression
T22289 39643-39645 IN denotes of
T22290 39646-39650 NN denotes Lef1
T22291 39650-39651 -RRB- denotes )
T22292 39660-39667 JJ denotes ectopic
T22293 39668-39677 NNS denotes follicles
T22294 39678-39680 IN denotes in
T22295 39681-39685 CC denotes both
T22296 39686-39691 NN denotes mouse
T22297 39702-39706 NN denotes skin
T22298 39692-39695 CC denotes and
T22299 39696-39701 NN denotes chick
T22300 39707-39708 -LRB- denotes [
T22301 39708-39710 CD denotes 25
T22302 39710-39711 SYM denotes
T22303 39711-39713 CD denotes 27
T22304 39713-39714 -RRB- denotes ]
T22305 39714-39715 . denotes .
T22306 39715-39955 sentence denotes Conversely, down-regulation of β-catenin signaling (through Lef1 knock-out, ectopic expression of Wnt inhibitor Dkk1 or conditional deletion of β-catenin in epidermis) results in loss of vibrissae and some pelage follicles in mice [28–30].
T22307 39716-39726 RB denotes Conversely
T22308 39884-39891 VBZ denotes results
T22309 39726-39728 , denotes ,
T22310 39728-39732 JJ denotes down
T22311 39733-39743 NN denotes regulation
T22312 39732-39733 HYPH denotes -
T22313 39744-39746 IN denotes of
T22314 39747-39748 NN denotes β
T22315 39749-39756 NN denotes catenin
T22316 39748-39749 HYPH denotes -
T22317 39757-39766 NN denotes signaling
T22318 39767-39768 -LRB- denotes (
T22319 39768-39775 IN denotes through
T22320 39776-39780 NN denotes Lef1
T22321 39781-39786 VB denotes knock
T22322 39800-39810 NN denotes expression
T22323 39786-39787 HYPH denotes -
T22324 39787-39790 RP denotes out
T22325 39790-39792 , denotes ,
T22326 39792-39799 JJ denotes ectopic
T22327 39811-39813 IN denotes of
T22328 39814-39817 NN denotes Wnt
T22329 39818-39827 NN denotes inhibitor
T22330 39828-39832 NN denotes Dkk1
T22331 39833-39835 CC denotes or
T22332 39836-39847 JJ denotes conditional
T22333 39848-39856 NN denotes deletion
T22334 39857-39859 IN denotes of
T22335 39860-39861 NN denotes β
T22336 39862-39869 NN denotes catenin
T22337 39861-39862 HYPH denotes -
T22338 39870-39872 IN denotes in
T22339 39873-39882 NN denotes epidermis
T22340 39882-39883 -RRB- denotes )
T22341 39892-39894 IN denotes in
T22342 39895-39899 NN denotes loss
T22343 39900-39902 IN denotes of
T22344 39903-39912 NNS denotes vibrissae
T22345 39913-39916 CC denotes and
T22346 39917-39921 DT denotes some
T22347 39929-39938 NNS denotes follicles
T22348 39922-39928 NN denotes pelage
T22349 39939-39941 IN denotes in
T22350 39942-39946 NNS denotes mice
T22351 39947-39948 -LRB- denotes [
T22352 39948-39950 CD denotes 28
T22353 39950-39951 SYM denotes
T22354 39951-39953 CD denotes 30
T22355 39953-39954 -RRB- denotes ]
T22356 39954-39955 . denotes .
T22357 39955-40449 sentence denotes Our finding that K14-driven Apc loss in embryonic ectoderm resulted in irregularly spaced and often tightly clustered abnormal hair placode initiation and follicle morphogenesis (Figures 4F, 5B, 5D, and 5F) as well as in the development of multiple tooth buds (Figure 4O and 4P), is in line with the effects seen in activation of epithelial β-catenin signaling during placode formation, indicating the role of Apc in specification of embryonic ectodermal stem cells to produce a hair follicle.
T22358 39956-39959 PRP$ denotes Our
T22359 39960-39967 NN denotes finding
T22360 40236-40238 VBZ denotes is
T22361 39968-39972 IN denotes that
T22362 40015-40023 VBD denotes resulted
T22363 39973-39976 NN denotes K14
T22364 39977-39983 VBN denotes driven
T22365 39976-39977 HYPH denotes -
T22366 39988-39992 NN denotes loss
T22367 39984-39987 NN denotes Apc
T22368 39993-39995 IN denotes in
T22369 39996-40005 JJ denotes embryonic
T22370 40006-40014 NN denotes ectoderm
T22371 40024-40026 IN denotes in
T22372 40027-40038 RB denotes irregularly
T22373 40039-40045 VBN denotes spaced
T22374 40096-40106 NN denotes initiation
T22375 40046-40049 CC denotes and
T22376 40050-40055 RB denotes often
T22377 40064-40073 VBN denotes clustered
T22378 40056-40063 RB denotes tightly
T22379 40074-40082 JJ denotes abnormal
T22380 40083-40087 NN denotes hair
T22381 40088-40095 NN denotes placode
T22382 40107-40110 CC denotes and
T22383 40111-40119 NN denotes follicle
T22384 40120-40133 NN denotes morphogenesis
T22385 40134-40135 -LRB- denotes (
T22386 40143-40145 NN denotes 4F
T22387 40135-40142 NNS denotes Figures
T22388 40145-40147 , denotes ,
T22389 40147-40149 NN denotes 5B
T22390 40149-40151 , denotes ,
T22391 40151-40153 NN denotes 5D
T22392 40153-40155 , denotes ,
T22393 40155-40158 CC denotes and
T22394 40159-40161 NN denotes 5F
T22395 40161-40162 -RRB- denotes )
T22396 40163-40165 RB denotes as
T22397 40171-40173 IN denotes as
T22398 40166-40170 RB denotes well
T22399 40174-40176 IN denotes in
T22400 40177-40180 DT denotes the
T22401 40181-40192 NN denotes development
T22402 40193-40195 IN denotes of
T22403 40196-40204 JJ denotes multiple
T22404 40211-40215 NNS denotes buds
T22405 40205-40210 NN denotes tooth
T22406 40216-40217 -LRB- denotes (
T22407 40224-40226 NN denotes 4O
T22408 40217-40223 NN denotes Figure
T22409 40227-40230 CC denotes and
T22410 40231-40233 NN denotes 4P
T22411 40233-40234 -RRB- denotes )
T22412 40234-40236 , denotes ,
T22413 40239-40241 IN denotes in
T22414 40242-40246 NN denotes line
T22415 40247-40251 IN denotes with
T22416 40252-40255 DT denotes the
T22417 40256-40263 NNS denotes effects
T22418 40264-40268 VBN denotes seen
T22419 40269-40271 IN denotes in
T22420 40272-40282 NN denotes activation
T22421 40283-40285 IN denotes of
T22422 40286-40296 JJ denotes epithelial
T22423 40307-40316 NN denotes signaling
T22424 40297-40298 NN denotes β
T22425 40299-40306 NN denotes catenin
T22426 40298-40299 HYPH denotes -
T22427 40317-40323 IN denotes during
T22428 40324-40331 NN denotes placode
T22429 40332-40341 NN denotes formation
T22430 40341-40343 , denotes ,
T22431 40343-40353 VBG denotes indicating
T22432 40354-40357 DT denotes the
T22433 40358-40362 NN denotes role
T22434 40363-40365 IN denotes of
T22435 40366-40369 NN denotes Apc
T22436 40370-40372 IN denotes in
T22437 40373-40386 NN denotes specification
T22438 40387-40389 IN denotes of
T22439 40390-40399 JJ denotes embryonic
T22440 40416-40421 NNS denotes cells
T22441 40400-40410 JJ denotes ectodermal
T22442 40411-40415 NN denotes stem
T22443 40422-40424 TO denotes to
T22444 40425-40432 VB denotes produce
T22445 40433-40434 DT denotes a
T22446 40440-40448 NN denotes follicle
T22447 40435-40439 NN denotes hair
T22448 40448-40449 . denotes .
T22449 40449-40783 sentence denotes Given the role of Apc in down-regulation of β-catenin, loss of Apc would inevitably lead to altered expression of β-catenin in ectodermal cells during the hair placode formation, giving rise to aberrant follicular growth throughout the embryonic epidermis, including the footpads, where normally hairless (Figure 5B, 5D, 5F, and 5H).
T22450 40450-40455 VBN denotes Given
T22451 40534-40538 VB denotes lead
T22452 40456-40459 DT denotes the
T22453 40460-40464 NN denotes role
T22454 40465-40467 IN denotes of
T22455 40468-40471 NN denotes Apc
T22456 40472-40474 IN denotes in
T22457 40475-40479 RB denotes down
T22458 40480-40490 NN denotes regulation
T22459 40479-40480 HYPH denotes -
T22460 40491-40493 IN denotes of
T22461 40494-40495 NN denotes β
T22462 40496-40503 NN denotes catenin
T22463 40495-40496 HYPH denotes -
T22464 40503-40505 , denotes ,
T22465 40505-40509 NN denotes loss
T22466 40510-40512 IN denotes of
T22467 40513-40516 NNP denotes Apc
T22468 40517-40522 MD denotes would
T22469 40523-40533 RB denotes inevitably
T22470 40539-40541 IN denotes to
T22471 40542-40549 JJ denotes altered
T22472 40550-40560 NN denotes expression
T22473 40561-40563 IN denotes of
T22474 40564-40565 NN denotes β
T22475 40566-40573 NN denotes catenin
T22476 40565-40566 HYPH denotes -
T22477 40574-40576 IN denotes in
T22478 40577-40587 JJ denotes ectodermal
T22479 40588-40593 NNS denotes cells
T22480 40594-40600 IN denotes during
T22481 40601-40604 DT denotes the
T22482 40618-40627 NN denotes formation
T22483 40605-40609 NN denotes hair
T22484 40610-40617 NN denotes placode
T22485 40627-40629 , denotes ,
T22486 40629-40635 VBG denotes giving
T22487 40636-40640 NN denotes rise
T22488 40641-40643 IN denotes to
T22489 40644-40652 JJ denotes aberrant
T22490 40664-40670 NN denotes growth
T22491 40653-40663 JJ denotes follicular
T22492 40671-40681 IN denotes throughout
T22493 40682-40685 DT denotes the
T22494 40696-40705 NN denotes epidermis
T22495 40686-40695 JJ denotes embryonic
T22496 40705-40707 , denotes ,
T22497 40707-40716 VBG denotes including
T22498 40717-40720 DT denotes the
T22499 40721-40729 NNS denotes footpads
T22500 40729-40731 , denotes ,
T22501 40731-40736 WRB denotes where
T22502 40746-40754 JJ denotes hairless
T22503 40737-40745 RB denotes normally
T22504 40755-40756 -LRB- denotes (
T22505 40763-40765 NN denotes 5B
T22506 40756-40762 NN denotes Figure
T22507 40765-40767 , denotes ,
T22508 40767-40769 NN denotes 5D
T22509 40769-40771 , denotes ,
T22510 40771-40773 NN denotes 5F
T22511 40773-40775 , denotes ,
T22512 40775-40778 CC denotes and
T22513 40779-40781 NN denotes 5H
T22514 40781-40782 -RRB- denotes )
T22515 40782-40783 . denotes .
T22516 40783-41030 sentence denotes Of interest are the phenotypic similarities and differences between our KA mutant mice and the previously described K14-ΔN87βcat transgenic mice expressing stable β-catenin under the control of K14 promoter [25] and K14-Lef1 transgenic mice [27].
T22517 40784-40786 IN denotes Of
T22518 40796-40799 VBP denotes are
T22519 40787-40795 NN denotes interest
T22520 40800-40803 DT denotes the
T22521 40815-40827 NNS denotes similarities
T22522 40804-40814 JJ denotes phenotypic
T22523 40828-40831 CC denotes and
T22524 40832-40843 NNS denotes differences
T22525 40844-40851 IN denotes between
T22526 40852-40855 PRP$ denotes our
T22527 40866-40870 NNS denotes mice
T22528 40856-40858 NN denotes KA
T22529 40859-40865 JJ denotes mutant
T22530 40871-40874 CC denotes and
T22531 40875-40878 DT denotes the
T22532 40924-40928 NNS denotes mice
T22533 40879-40889 RB denotes previously
T22534 40890-40899 VBN denotes described
T22535 40900-40903 NN denotes K14
T22536 40904-40912 NN denotes ΔN87βcat
T22537 40903-40904 HYPH denotes -
T22538 40913-40923 JJ denotes transgenic
T22539 40929-40939 VBG denotes expressing
T22540 40940-40946 JJ denotes stable
T22541 40949-40956 NN denotes catenin
T22542 40947-40948 NN denotes β
T22543 40948-40949 HYPH denotes -
T22544 40957-40962 IN denotes under
T22545 40963-40966 DT denotes the
T22546 40967-40974 NN denotes control
T22547 40975-40977 IN denotes of
T22548 40978-40981 NN denotes K14
T22549 40982-40990 NN denotes promoter
T22550 40991-40992 -LRB- denotes [
T22551 40992-40994 CD denotes 25
T22552 40994-40995 -RRB- denotes ]
T22553 40996-40999 CC denotes and
T22554 41000-41003 NN denotes K14
T22555 41004-41008 NN denotes Lef1
T22556 41003-41004 HYPH denotes -
T22557 41020-41024 NNS denotes mice
T22558 41009-41019 JJ denotes transgenic
T22559 41025-41026 -LRB- denotes [
T22560 41026-41028 CD denotes 27
T22561 41028-41029 -RRB- denotes ]
T22562 41029-41030 . denotes .
T22563 41030-41147 sentence denotes Surprisingly, our mutant mice shared more similarities with the K14-Lef1 mice than the K14-ΔN87βcat transgenic mice.
T22564 41031-41043 RB denotes Surprisingly
T22565 41061-41067 VBD denotes shared
T22566 41043-41045 , denotes ,
T22567 41045-41048 PRP$ denotes our
T22568 41056-41060 NNS denotes mice
T22569 41049-41055 JJ denotes mutant
T22570 41068-41072 JJR denotes more
T22571 41073-41085 NNS denotes similarities
T22572 41086-41090 IN denotes with
T22573 41091-41094 DT denotes the
T22574 41104-41108 NNS denotes mice
T22575 41095-41098 NN denotes K14
T22576 41099-41103 NN denotes Lef1
T22577 41098-41099 HYPH denotes -
T22578 41109-41113 IN denotes than
T22579 41114-41117 DT denotes the
T22580 41142-41146 NNS denotes mice
T22581 41118-41121 NN denotes K14
T22582 41122-41130 NN denotes ΔN87βcat
T22583 41121-41122 HYPH denotes -
T22584 41131-41141 JJ denotes transgenic
T22585 41146-41147 . denotes .
T22586 41147-41288 sentence denotes For example, the KA mutant mice displayed the disoriented and short, curly whiskers seen in K14-Lef1but not in K14-ΔN87βcat transgenic mice.
T22587 41148-41151 IN denotes For
T22588 41180-41189 VBD denotes displayed
T22589 41152-41159 NN denotes example
T22590 41159-41161 , denotes ,
T22591 41161-41164 DT denotes the
T22592 41175-41179 NNS denotes mice
T22593 41165-41167 NN denotes KA
T22594 41168-41174 JJ denotes mutant
T22595 41190-41193 DT denotes the
T22596 41223-41231 NNS denotes whiskers
T22597 41194-41205 JJ denotes disoriented
T22598 41206-41209 CC denotes and
T22599 41210-41215 JJ denotes short
T22600 41215-41217 , denotes ,
T22601 41217-41222 JJ denotes curly
T22602 41232-41236 VBN denotes seen
T22603 41237-41239 IN denotes in
T22604 41240-41243 NN denotes K14
T22605 41244-41251 NN denotes Lef1but
T22606 41243-41244 HYPH denotes -
T22607 41252-41255 RB denotes not
T22608 41256-41258 IN denotes in
T22609 41259-41262 NN denotes K14
T22610 41263-41271 NN denotes ΔN87βcat
T22611 41262-41263 HYPH denotes -
T22612 41283-41287 NNS denotes mice
T22613 41272-41282 JJ denotes transgenic
T22614 41287-41288 . denotes .
T22615 41288-41574 sentence denotes In addition, KA mutant mice displayed a disorganized hair coat beginning with the emergence of neonatal hairs, similar to that observed in K14-Lef1 mice, whereas in K14-ΔN87βcat mice, embryonic hair follicle morphogenesis was unaffected and other skin changes only emerged postnatally.
T22616 41289-41291 IN denotes In
T22617 41317-41326 VBD denotes displayed
T22618 41292-41300 NN denotes addition
T22619 41300-41302 , denotes ,
T22620 41302-41304 NN denotes KA
T22621 41312-41316 NNS denotes mice
T22622 41305-41311 JJ denotes mutant
T22623 41327-41328 DT denotes a
T22624 41347-41351 NN denotes coat
T22625 41329-41341 JJ denotes disorganized
T22626 41342-41346 NN denotes hair
T22627 41352-41361 VBG denotes beginning
T22628 41362-41366 IN denotes with
T22629 41367-41370 DT denotes the
T22630 41371-41380 NN denotes emergence
T22631 41381-41383 IN denotes of
T22632 41384-41392 JJ denotes neonatal
T22633 41393-41398 NNS denotes hairs
T22634 41398-41400 , denotes ,
T22635 41400-41407 JJ denotes similar
T22636 41408-41410 IN denotes to
T22637 41411-41415 DT denotes that
T22638 41416-41424 VBN denotes observed
T22639 41425-41427 IN denotes in
T22640 41428-41431 NN denotes K14
T22641 41432-41436 NN denotes Lef1
T22642 41431-41432 HYPH denotes -
T22643 41437-41441 NNS denotes mice
T22644 41441-41443 , denotes ,
T22645 41443-41450 IN denotes whereas
T22646 41511-41514 VBD denotes was
T22647 41451-41453 IN denotes in
T22648 41454-41457 NN denotes K14
T22649 41458-41466 NN denotes ΔN87βcat
T22650 41457-41458 HYPH denotes -
T22651 41467-41471 NNS denotes mice
T22652 41471-41473 , denotes ,
T22653 41473-41482 JJ denotes embryonic
T22654 41497-41510 NN denotes morphogenesis
T22655 41483-41487 NN denotes hair
T22656 41488-41496 NN denotes follicle
T22657 41515-41525 JJ denotes unaffected
T22658 41526-41529 CC denotes and
T22659 41530-41535 JJ denotes other
T22660 41541-41548 NNS denotes changes
T22661 41536-41540 NN denotes skin
T22662 41554-41561 VBD denotes emerged
T22663 41549-41553 RB denotes only
T22664 41562-41573 RB denotes postnatally
T22665 41573-41574 . denotes .
T22666 41574-41679 sentence denotes The reason for this difference could be attributed to one or all of three possible contributing factors.
T22667 41575-41578 DT denotes The
T22668 41579-41585 NN denotes reason
T22669 41615-41625 VBN denotes attributed
T22670 41586-41589 IN denotes for
T22671 41590-41594 DT denotes this
T22672 41595-41605 NN denotes difference
T22673 41606-41611 MD denotes could
T22674 41612-41614 VB denotes be
T22675 41626-41628 IN denotes to
T22676 41629-41632 CD denotes one
T22677 41633-41635 CC denotes or
T22678 41636-41639 DT denotes all
T22679 41640-41642 IN denotes of
T22680 41643-41648 CD denotes three
T22681 41671-41678 NNS denotes factors
T22682 41649-41657 JJ denotes possible
T22683 41658-41670 VBG denotes contributing
T22684 41678-41679 . denotes .
T22685 41679-41906 sentence denotes (1) Although the K14 promoter itself is known to initiate the expression at E9.5 and elevated dramatically by E13.5–E14.5 [19,31], many factors could influence the expression of promoter/transgene construct in transgenic mice.
T22686 41680-41681 -LRB- denotes (
T22687 41681-41682 LS denotes 1
T22688 41830-41839 VB denotes influence
T22689 41682-41683 -RRB- denotes )
T22690 41684-41692 IN denotes Although
T22691 41720-41725 VBN denotes known
T22692 41693-41696 DT denotes the
T22693 41701-41709 NN denotes promoter
T22694 41697-41700 NN denotes K14
T22695 41710-41716 PRP denotes itself
T22696 41717-41719 VBZ denotes is
T22697 41726-41728 TO denotes to
T22698 41729-41737 VB denotes initiate
T22699 41738-41741 DT denotes the
T22700 41742-41752 NN denotes expression
T22701 41753-41755 IN denotes at
T22702 41756-41760 NN denotes E9.5
T22703 41761-41764 CC denotes and
T22704 41765-41773 VBN denotes elevated
T22705 41774-41786 RB denotes dramatically
T22706 41787-41789 IN denotes by
T22707 41790-41795 NN denotes E13.5
T22708 41795-41796 SYM denotes
T22709 41796-41801 NN denotes E14.5
T22710 41802-41803 -LRB- denotes [
T22711 41806-41808 CD denotes 31
T22712 41803-41805 CD denotes 19
T22713 41805-41806 , denotes ,
T22714 41808-41809 -RRB- denotes ]
T22715 41809-41811 , denotes ,
T22716 41811-41815 JJ denotes many
T22717 41816-41823 NNS denotes factors
T22718 41824-41829 MD denotes could
T22719 41840-41843 DT denotes the
T22720 41844-41854 NN denotes expression
T22721 41855-41857 IN denotes of
T22722 41858-41866 NN denotes promoter
T22723 41867-41876 NN denotes transgene
T22724 41866-41867 HYPH denotes /
T22725 41877-41886 NN denotes construct
T22726 41887-41889 IN denotes in
T22727 41890-41900 JJ denotes transgenic
T22728 41901-41905 NNS denotes mice
T22729 41905-41906 . denotes .
T22730 41906-42021 sentence denotes One of the most important considerations has to do with the integration site of the transgene in the mouse genome.
T22731 41907-41910 CD denotes One
T22732 41948-41951 VBZ denotes has
T22733 41911-41913 IN denotes of
T22734 41914-41917 DT denotes the
T22735 41933-41947 NNS denotes considerations
T22736 41918-41922 RBS denotes most
T22737 41923-41932 JJ denotes important
T22738 41952-41954 TO denotes to
T22739 41955-41957 VB denotes do
T22740 41958-41962 IN denotes with
T22741 41963-41966 DT denotes the
T22742 41979-41983 NN denotes site
T22743 41967-41978 NN denotes integration
T22744 41984-41986 IN denotes of
T22745 41987-41990 DT denotes the
T22746 41991-42000 NN denotes transgene
T22747 42001-42003 IN denotes in
T22748 42004-42007 DT denotes the
T22749 42014-42020 NN denotes genome
T22750 42008-42013 NN denotes mouse
T22751 42020-42021 . denotes .
T22752 42021-42144 sentence denotes Depending on the location of integration, the transcriptional activity of even the same transgene could vary considerably.
T22753 42022-42031 VBG denotes Depending
T22754 42126-42130 VB denotes vary
T22755 42032-42034 IN denotes on
T22756 42035-42038 DT denotes the
T22757 42039-42047 NN denotes location
T22758 42048-42050 IN denotes of
T22759 42051-42062 NN denotes integration
T22760 42062-42064 , denotes ,
T22761 42064-42067 DT denotes the
T22762 42084-42092 NN denotes activity
T22763 42068-42083 JJ denotes transcriptional
T22764 42093-42095 IN denotes of
T22765 42096-42100 RB denotes even
T22766 42110-42119 NN denotes transgene
T22767 42101-42104 DT denotes the
T22768 42105-42109 JJ denotes same
T22769 42120-42125 MD denotes could
T22770 42131-42143 RB denotes considerably
T22771 42143-42144 . denotes .
T22772 42144-42333 sentence denotes It is possible that the apparent lack of ΔN87βcat function in embryogenesis could be due to the delayed or weak expression of the K14-ΔN87βcat transgene compared to the intrinsic promoter.
T22773 42145-42147 PRP denotes It
T22774 42148-42150 VBZ denotes is
T22775 42151-42159 JJ denotes possible
T22776 42160-42164 IN denotes that
T22777 42227-42229 VB denotes be
T22778 42165-42168 DT denotes the
T22779 42178-42182 NN denotes lack
T22780 42169-42177 JJ denotes apparent
T22781 42183-42185 IN denotes of
T22782 42186-42194 NN denotes ΔN87βcat
T22783 42195-42203 NN denotes function
T22784 42204-42206 IN denotes in
T22785 42207-42220 NN denotes embryogenesis
T22786 42221-42226 MD denotes could
T22787 42230-42233 IN denotes due
T22788 42234-42236 IN denotes to
T22789 42237-42240 DT denotes the
T22790 42257-42267 NN denotes expression
T22791 42241-42248 VBN denotes delayed
T22792 42249-42251 CC denotes or
T22793 42252-42256 JJ denotes weak
T22794 42268-42270 IN denotes of
T22795 42271-42274 DT denotes the
T22796 42288-42297 NN denotes transgene
T22797 42275-42278 NN denotes K14
T22798 42279-42287 NN denotes ΔN87βcat
T22799 42278-42279 HYPH denotes -
T22800 42298-42306 VBN denotes compared
T22801 42307-42309 IN denotes to
T22802 42310-42313 DT denotes the
T22803 42324-42332 NN denotes promoter
T22804 42314-42323 JJ denotes intrinsic
T22805 42332-42333 . denotes .
T22806 42333-42589 sentence denotes In contrast, Cre-mediated recombination is seen in E13.5 skin of K14-cre transgenic mice used in this study [16] and K14-cre–mediated truncation of the Apc gene is likely to have occurred by then, in time for the second wave of hair follicle morphgenesis.
T22807 42334-42336 IN denotes In
T22808 42377-42381 VBN denotes seen
T22809 42337-42345 NN denotes contrast
T22810 42345-42347 , denotes ,
T22811 42347-42350 NN denotes Cre
T22812 42351-42359 JJ denotes mediated
T22813 42350-42351 HYPH denotes -
T22814 42360-42373 NN denotes recombination
T22815 42374-42376 VBZ denotes is
T22816 42382-42384 IN denotes in
T22817 42385-42390 NN denotes E13.5
T22818 42391-42395 NN denotes skin
T22819 42396-42398 IN denotes of
T22820 42399-42402 NN denotes K14
T22821 42403-42406 NN denotes cre
T22822 42402-42403 HYPH denotes -
T22823 42418-42422 NNS denotes mice
T22824 42407-42417 JJ denotes transgenic
T22825 42423-42427 VBN denotes used
T22826 42428-42430 IN denotes in
T22827 42431-42435 DT denotes this
T22828 42436-42441 NN denotes study
T22829 42442-42443 -LRB- denotes [
T22830 42443-42445 CD denotes 16
T22831 42445-42446 -RRB- denotes ]
T22832 42447-42450 CC denotes and
T22833 42451-42454 NN denotes K14
T22834 42455-42458 NN denotes cre
T22835 42454-42455 HYPH denotes -
T22836 42459-42467 JJ denotes mediated
T22837 42458-42459 HYPH denotes
T22838 42468-42478 NN denotes truncation
T22839 42495-42497 VBZ denotes is
T22840 42479-42481 IN denotes of
T22841 42482-42485 DT denotes the
T22842 42490-42494 NN denotes gene
T22843 42486-42489 NN denotes Apc
T22844 42498-42504 JJ denotes likely
T22845 42505-42507 TO denotes to
T22846 42513-42521 VBN denotes occurred
T22847 42508-42512 VB denotes have
T22848 42522-42524 IN denotes by
T22849 42525-42529 RB denotes then
T22850 42529-42531 , denotes ,
T22851 42531-42533 IN denotes in
T22852 42534-42538 NN denotes time
T22853 42539-42542 IN denotes for
T22854 42543-42546 DT denotes the
T22855 42554-42558 NN denotes wave
T22856 42547-42553 JJ denotes second
T22857 42559-42561 IN denotes of
T22858 42562-42566 NN denotes hair
T22859 42567-42575 NN denotes follicle
T22860 42576-42588 NN denotes morphgenesis
T22861 42588-42589 . denotes .
T22862 42589-42808 sentence denotes (2) Another important fact is that in the aforementioned transgenic model the overexpression of transgene is confined to the basal cells of the epidermis and the ORS of hair follicles, where the K14 promoter is active.
T22863 42590-42591 -LRB- denotes (
T22864 42591-42592 LS denotes 2
T22865 42617-42619 VBZ denotes is
T22866 42592-42593 -RRB- denotes )
T22867 42594-42601 DT denotes Another
T22868 42612-42616 NN denotes fact
T22869 42602-42611 JJ denotes important
T22870 42620-42624 IN denotes that
T22871 42699-42707 VBN denotes confined
T22872 42625-42627 IN denotes in
T22873 42628-42631 DT denotes the
T22874 42658-42663 NN denotes model
T22875 42632-42646 JJ denotes aforementioned
T22876 42647-42657 JJ denotes transgenic
T22877 42664-42667 DT denotes the
T22878 42668-42682 NN denotes overexpression
T22879 42683-42685 IN denotes of
T22880 42686-42695 NN denotes transgene
T22881 42696-42698 VBZ denotes is
T22882 42708-42710 IN denotes to
T22883 42711-42714 DT denotes the
T22884 42721-42726 NNS denotes cells
T22885 42715-42720 JJ denotes basal
T22886 42727-42729 IN denotes of
T22887 42730-42733 DT denotes the
T22888 42734-42743 NN denotes epidermis
T22889 42744-42747 CC denotes and
T22890 42748-42751 DT denotes the
T22891 42752-42755 NN denotes ORS
T22892 42756-42758 IN denotes of
T22893 42759-42763 NN denotes hair
T22894 42764-42773 NNS denotes follicles
T22895 42773-42775 , denotes ,
T22896 42775-42780 WRB denotes where
T22897 42798-42800 VBZ denotes is
T22898 42781-42784 DT denotes the
T22899 42789-42797 NN denotes promoter
T22900 42785-42788 NN denotes K14
T22901 42801-42807 JJ denotes active
T22902 42807-42808 . denotes .
T22903 42808-42917 sentence denotes The expression of transgene is hence transient and stops once K14-expressing cells terminally differentiate.
T22904 42809-42812 DT denotes The
T22905 42813-42823 NN denotes expression
T22906 42837-42839 VBZ denotes is
T22907 42824-42826 IN denotes of
T22908 42827-42836 NN denotes transgene
T22909 42840-42845 RB denotes hence
T22910 42846-42855 JJ denotes transient
T22911 42856-42859 CC denotes and
T22912 42860-42865 VBZ denotes stops
T22913 42866-42870 IN denotes once
T22914 42903-42916 VBP denotes differentiate
T22915 42871-42874 NN denotes K14
T22916 42875-42885 VBG denotes expressing
T22917 42874-42875 HYPH denotes -
T22918 42886-42891 NNS denotes cells
T22919 42892-42902 RB denotes terminally
T22920 42916-42917 . denotes .
T22921 42917-43133 sentence denotes In contrast, in our model, K14-cre–mediated deletion of Apc would result in Apc mutation not only in K14 promoter active cells, but remain so in all cell layers that derived from the K14 promoter active progenitors.
T22922 42918-42920 IN denotes In
T22923 42984-42990 VB denotes result
T22924 42921-42929 NN denotes contrast
T22925 42929-42931 , denotes ,
T22926 42931-42933 IN denotes in
T22927 42934-42937 PRP$ denotes our
T22928 42938-42943 NN denotes model
T22929 42943-42945 , denotes ,
T22930 42945-42948 NN denotes K14
T22931 42949-42952 NN denotes cre
T22932 42948-42949 HYPH denotes -
T22933 42953-42961 JJ denotes mediated
T22934 42952-42953 HYPH denotes
T22935 42962-42970 NN denotes deletion
T22936 42971-42973 IN denotes of
T22937 42974-42977 NN denotes Apc
T22938 42978-42983 MD denotes would
T22939 42991-42993 IN denotes in
T22940 42994-42997 NN denotes Apc
T22941 42998-43006 NN denotes mutation
T22942 43007-43010 RB denotes not
T22943 43016-43018 IN denotes in
T22944 43011-43015 RB denotes only
T22945 43019-43022 NN denotes K14
T22946 43039-43044 NNS denotes cells
T22947 43023-43031 NN denotes promoter
T22948 43032-43038 JJ denotes active
T22949 43044-43046 , denotes ,
T22950 43046-43049 CC denotes but
T22951 43050-43056 VBP denotes remain
T22952 43057-43059 RB denotes so
T22953 43060-43062 IN denotes in
T22954 43063-43066 DT denotes all
T22955 43072-43078 NNS denotes layers
T22956 43067-43071 NN denotes cell
T22957 43079-43083 WDT denotes that
T22958 43084-43091 VBN denotes derived
T22959 43092-43096 IN denotes from
T22960 43097-43100 DT denotes the
T22961 43121-43132 NNS denotes progenitors
T22962 43101-43104 NN denotes K14
T22963 43105-43113 NN denotes promoter
T22964 43114-43120 JJ denotes active
T22965 43132-43133 . denotes .
T22966 43133-43232 sentence denotes These derivatives include the suprabasal epidermis and the entire epithelium of the hair follicle.
T22967 43134-43139 DT denotes These
T22968 43140-43151 NNS denotes derivatives
T22969 43152-43159 VBP denotes include
T22970 43160-43163 DT denotes the
T22971 43175-43184 NN denotes epidermis
T22972 43164-43174 JJ denotes suprabasal
T22973 43185-43188 CC denotes and
T22974 43189-43192 DT denotes the
T22975 43200-43210 NN denotes epithelium
T22976 43193-43199 JJ denotes entire
T22977 43211-43213 IN denotes of
T22978 43214-43217 DT denotes the
T22979 43223-43231 NN denotes follicle
T22980 43218-43222 NN denotes hair
T22981 43231-43232 . denotes .
T22982 43232-43346 sentence denotes Stabilization of β-catenin in a broader population of cells could account for some of the phenotypic differences.
T22983 43233-43246 NN denotes Stabilization
T22984 43299-43306 VB denotes account
T22985 43247-43249 IN denotes of
T22986 43250-43251 NN denotes β
T22987 43252-43259 NN denotes catenin
T22988 43251-43252 HYPH denotes -
T22989 43260-43262 IN denotes in
T22990 43263-43264 DT denotes a
T22991 43273-43283 NN denotes population
T22992 43265-43272 JJR denotes broader
T22993 43284-43286 IN denotes of
T22994 43287-43292 NNS denotes cells
T22995 43293-43298 MD denotes could
T22996 43307-43310 IN denotes for
T22997 43311-43315 DT denotes some
T22998 43316-43318 IN denotes of
T22999 43319-43322 DT denotes the
T23000 43334-43345 NNS denotes differences
T23001 43323-43333 JJ denotes phenotypic
T23002 43345-43346 . denotes .
T23003 43346-43483 sentence denotes However, we did not detect any elevated β-catenin expression in either K1- or K6-positive differentiated cells in postnatal mutant skin.
T23004 43347-43354 RB denotes However
T23005 43367-43373 VB denotes detect
T23006 43354-43356 , denotes ,
T23007 43356-43358 PRP denotes we
T23008 43359-43362 VBD denotes did
T23009 43363-43366 RB denotes not
T23010 43374-43377 DT denotes any
T23011 43397-43407 NN denotes expression
T23012 43378-43386 JJ denotes elevated
T23013 43387-43388 NN denotes β
T23014 43389-43396 NN denotes catenin
T23015 43388-43389 HYPH denotes -
T23016 43408-43410 IN denotes in
T23017 43411-43417 CC denotes either
T23018 43452-43457 NNS denotes cells
T23019 43418-43420 NN denotes K1
T23020 43428-43436 JJ denotes positive
T23021 43420-43421 HYPH denotes -
T23022 43422-43424 CC denotes or
T23023 43425-43427 NN denotes K6
T23024 43427-43428 HYPH denotes -
T23025 43437-43451 VBN denotes differentiated
T23026 43458-43460 IN denotes in
T23027 43461-43470 JJ denotes postnatal
T23028 43478-43482 NN denotes skin
T23029 43471-43477 JJ denotes mutant
T23030 43482-43483 . denotes .
T23031 43483-43723 sentence denotes This indicates that despite the absence of Apc and potential stabilization of β-catenin in derivatives of K14-expressing progenitors, elevated β-catenin expression, and subsequent cell fate determination may only take place in basal cells.
T23032 43484-43488 DT denotes This
T23033 43489-43498 VBZ denotes indicates
T23034 43499-43503 IN denotes that
T23035 43697-43701 VB denotes take
T23036 43504-43511 IN denotes despite
T23037 43512-43515 DT denotes the
T23038 43516-43523 NN denotes absence
T23039 43524-43526 IN denotes of
T23040 43527-43530 NN denotes Apc
T23041 43531-43534 CC denotes and
T23042 43535-43544 JJ denotes potential
T23043 43545-43558 NN denotes stabilization
T23044 43559-43561 IN denotes of
T23045 43562-43563 NN denotes β
T23046 43564-43571 NN denotes catenin
T23047 43563-43564 HYPH denotes -
T23048 43572-43574 IN denotes in
T23049 43575-43586 NNS denotes derivatives
T23050 43587-43589 IN denotes of
T23051 43590-43593 NN denotes K14
T23052 43594-43604 VBG denotes expressing
T23053 43593-43594 HYPH denotes -
T23054 43605-43616 NNS denotes progenitors
T23055 43616-43618 , denotes ,
T23056 43618-43626 JJ denotes elevated
T23057 43637-43647 NN denotes expression
T23058 43627-43628 NN denotes β
T23059 43629-43636 NN denotes catenin
T23060 43628-43629 HYPH denotes -
T23061 43647-43649 , denotes ,
T23062 43649-43652 CC denotes and
T23063 43653-43663 JJ denotes subsequent
T23064 43674-43687 NN denotes determination
T23065 43664-43668 NN denotes cell
T23066 43669-43673 NN denotes fate
T23067 43688-43691 MD denotes may
T23068 43692-43696 RB denotes only
T23069 43702-43707 NN denotes place
T23070 43708-43710 IN denotes in
T23071 43711-43716 JJ denotes basal
T23072 43717-43722 NNS denotes cells
T23073 43722-43723 . denotes .
T23074 43723-43938 sentence denotes (3) We cannot exclude the possibility that given the multifunctional properties of Apc, disruption of its functions other than down-regulation of β-catenin may also have contributed to the observed overt phenotype.
T23075 43724-43725 -LRB- denotes (
T23076 43725-43726 LS denotes 3
T23077 43738-43745 VB denotes exclude
T23078 43726-43727 -RRB- denotes )
T23079 43728-43730 PRP denotes We
T23080 43731-43734 MD denotes can
T23081 43734-43737 RB denotes not
T23082 43746-43749 DT denotes the
T23083 43750-43761 NN denotes possibility
T23084 43762-43766 IN denotes that
T23085 43894-43905 VBN denotes contributed
T23086 43767-43772 VBN denotes given
T23087 43773-43776 DT denotes the
T23088 43793-43803 NNS denotes properties
T23089 43777-43792 JJ denotes multifunctional
T23090 43804-43806 IN denotes of
T23091 43807-43810 NN denotes Apc
T23092 43810-43812 , denotes ,
T23093 43812-43822 NN denotes disruption
T23094 43823-43825 IN denotes of
T23095 43826-43829 PRP$ denotes its
T23096 43830-43839 NNS denotes functions
T23097 43840-43845 JJ denotes other
T23098 43846-43850 IN denotes than
T23099 43851-43855 RB denotes down
T23100 43856-43866 NN denotes regulation
T23101 43855-43856 HYPH denotes -
T23102 43867-43869 IN denotes of
T23103 43870-43871 NN denotes β
T23104 43872-43879 NN denotes catenin
T23105 43871-43872 HYPH denotes -
T23106 43880-43883 MD denotes may
T23107 43884-43888 RB denotes also
T23108 43889-43893 VB denotes have
T23109 43906-43908 IN denotes to
T23110 43909-43912 DT denotes the
T23111 43928-43937 NN denotes phenotype
T23112 43913-43921 VBN denotes observed
T23113 43922-43927 JJ denotes overt
T23114 43937-43938 . denotes .
T23115 43938-44064 sentence denotes While some features of our mutant mice were similar to these transgenic mice, other phenotypic aspects were largely distinct.
T23116 43939-43944 IN denotes While
T23117 43978-43982 VBD denotes were
T23118 43945-43949 DT denotes some
T23119 43950-43958 NNS denotes features
T23120 43959-43961 IN denotes of
T23121 43962-43965 PRP$ denotes our
T23122 43973-43977 NNS denotes mice
T23123 43966-43972 JJ denotes mutant
T23124 44042-44046 VBD denotes were
T23125 43983-43990 JJ denotes similar
T23126 43991-43993 IN denotes to
T23127 43994-43999 DT denotes these
T23128 44011-44015 NNS denotes mice
T23129 44000-44010 JJ denotes transgenic
T23130 44015-44017 , denotes ,
T23131 44017-44022 JJ denotes other
T23132 44034-44041 NNS denotes aspects
T23133 44023-44033 JJ denotes phenotypic
T23134 44047-44054 RB denotes largely
T23135 44055-44063 JJ denotes distinct
T23136 44063-44064 . denotes .
T23137 44064-44299 sentence denotes In addition to aberrant hair follicle morphogenesis, K14-driven loss of Apc caused formation of multiple tooth buds that, like hair follicles, were known to develop through inductive interactions between the epithelium and mesenchyme.
T23138 44065-44067 IN denotes In
T23139 44141-44147 VBD denotes caused
T23140 44068-44076 NN denotes addition
T23141 44077-44079 IN denotes to
T23142 44080-44088 JJ denotes aberrant
T23143 44103-44116 NN denotes morphogenesis
T23144 44089-44093 NN denotes hair
T23145 44094-44102 NN denotes follicle
T23146 44116-44118 , denotes ,
T23147 44118-44121 NN denotes K14
T23148 44122-44128 JJ denotes driven
T23149 44121-44122 HYPH denotes -
T23150 44129-44133 NN denotes loss
T23151 44134-44136 IN denotes of
T23152 44137-44140 NN denotes Apc
T23153 44148-44157 NN denotes formation
T23154 44158-44160 IN denotes of
T23155 44161-44169 JJ denotes multiple
T23156 44176-44180 NNS denotes buds
T23157 44170-44175 NN denotes tooth
T23158 44181-44185 WDT denotes that
T23159 44213-44218 VBN denotes known
T23160 44185-44187 , denotes ,
T23161 44187-44191 IN denotes like
T23162 44192-44196 NN denotes hair
T23163 44197-44206 NNS denotes follicles
T23164 44206-44208 , denotes ,
T23165 44208-44212 VBD denotes were
T23166 44219-44221 TO denotes to
T23167 44222-44229 VB denotes develop
T23168 44230-44237 IN denotes through
T23169 44238-44247 JJ denotes inductive
T23170 44248-44260 NNS denotes interactions
T23171 44261-44268 IN denotes between
T23172 44269-44272 DT denotes the
T23173 44273-44283 NN denotes epithelium
T23174 44284-44287 CC denotes and
T23175 44288-44298 NN denotes mesenchyme
T23176 44298-44299 . denotes .
T23177 44299-44631 sentence denotes This observation was similar to the ectopic tooth buds found in animals misexpressing Lef1 [27], but more severe and was also present at birth, indicating the effect of Apc loss during the initiation of embryonic tooth development, which was evident by aberrant Shh expression in E15.5 embryonic oral epithelium (unpublished data).
T23178 44300-44304 DT denotes This
T23179 44305-44316 NN denotes observation
T23180 44317-44320 VBD denotes was
T23181 44321-44328 JJ denotes similar
T23182 44329-44331 IN denotes to
T23183 44332-44335 DT denotes the
T23184 44350-44354 NNS denotes buds
T23185 44336-44343 JJ denotes ectopic
T23186 44344-44349 NN denotes tooth
T23187 44355-44360 VBN denotes found
T23188 44361-44363 IN denotes in
T23189 44364-44371 NNS denotes animals
T23190 44372-44385 VBG denotes misexpressing
T23191 44386-44390 NN denotes Lef1
T23192 44391-44392 -LRB- denotes [
T23193 44392-44394 CD denotes 27
T23194 44394-44395 -RRB- denotes ]
T23195 44395-44397 , denotes ,
T23196 44397-44400 CC denotes but
T23197 44401-44405 RBR denotes more
T23198 44406-44412 JJ denotes severe
T23199 44413-44416 CC denotes and
T23200 44417-44420 VBD denotes was
T23201 44421-44425 RB denotes also
T23202 44426-44433 JJ denotes present
T23203 44434-44436 IN denotes at
T23204 44437-44442 NN denotes birth
T23205 44442-44444 , denotes ,
T23206 44444-44454 VBG denotes indicating
T23207 44455-44458 DT denotes the
T23208 44459-44465 NN denotes effect
T23209 44466-44468 IN denotes of
T23210 44469-44472 NN denotes Apc
T23211 44473-44477 NN denotes loss
T23212 44478-44484 IN denotes during
T23213 44485-44488 DT denotes the
T23214 44489-44499 NN denotes initiation
T23215 44500-44502 IN denotes of
T23216 44503-44512 JJ denotes embryonic
T23217 44519-44530 NN denotes development
T23218 44513-44518 NN denotes tooth
T23219 44530-44532 , denotes ,
T23220 44532-44537 WDT denotes which
T23221 44538-44541 VBD denotes was
T23222 44542-44549 JJ denotes evident
T23223 44550-44552 IN denotes by
T23224 44553-44561 JJ denotes aberrant
T23225 44566-44576 NN denotes expression
T23226 44562-44565 NN denotes Shh
T23227 44577-44579 IN denotes in
T23228 44580-44585 NN denotes E15.5
T23229 44601-44611 NN denotes epithelium
T23230 44586-44595 JJ denotes embryonic
T23231 44596-44600 JJ denotes oral
T23232 44612-44613 -LRB- denotes (
T23233 44625-44629 NNS denotes data
T23234 44613-44624 JJ denotes unpublished
T23235 44629-44630 -RRB- denotes )
T23236 44630-44631 . denotes .
T23237 44631-44803 sentence denotes It should be noted that although multiple tooth buds were histologically visible (Figure 4O and 4P), these teeth never broke out and the KA mutant mice appeared toothless.
T23238 44632-44634 PRP denotes It
T23239 44645-44650 VBN denotes noted
T23240 44635-44641 MD denotes should
T23241 44642-44644 VB denotes be
T23242 44651-44655 IN denotes that
T23243 44751-44756 VBD denotes broke
T23244 44656-44664 IN denotes although
T23245 44685-44689 VBD denotes were
T23246 44665-44673 JJ denotes multiple
T23247 44680-44684 NNS denotes buds
T23248 44674-44679 NN denotes tooth
T23249 44690-44704 RB denotes histologically
T23250 44705-44712 JJ denotes visible
T23251 44713-44714 -LRB- denotes (
T23252 44721-44723 NN denotes 4O
T23253 44714-44720 NN denotes Figure
T23254 44724-44727 CC denotes and
T23255 44728-44730 NN denotes 4P
T23256 44730-44731 -RRB- denotes )
T23257 44731-44733 , denotes ,
T23258 44733-44738 DT denotes these
T23259 44739-44744 NNS denotes teeth
T23260 44745-44750 RB denotes never
T23261 44757-44760 RP denotes out
T23262 44761-44764 CC denotes and
T23263 44765-44768 DT denotes the
T23264 44779-44783 NNS denotes mice
T23265 44769-44771 NN denotes KA
T23266 44772-44778 JJ denotes mutant
T23267 44784-44792 VBD denotes appeared
T23268 44793-44802 JJ denotes toothless
T23269 44802-44803 . denotes .
T23270 44803-44868 sentence denotes This unusual severe tooth defect is unique to these mutant mice.
T23271 44804-44808 DT denotes This
T23272 44830-44836 NN denotes defect
T23273 44809-44816 JJ denotes unusual
T23274 44817-44823 JJ denotes severe
T23275 44824-44829 NN denotes tooth
T23276 44837-44839 VBZ denotes is
T23277 44840-44846 JJ denotes unique
T23278 44847-44849 IN denotes to
T23279 44850-44855 DT denotes these
T23280 44863-44867 NNS denotes mice
T23281 44856-44862 JJ denotes mutant
T23282 44867-44868 . denotes .
T23283 44868-44965 sentence denotes In addition, neither of the two transgenic mice was postnatally lethal as in the KA mutant mice.
T23284 44869-44871 IN denotes In
T23285 44917-44920 VBD denotes was
T23286 44872-44880 NN denotes addition
T23287 44880-44882 , denotes ,
T23288 44882-44889 DT denotes neither
T23289 44890-44892 IN denotes of
T23290 44893-44896 DT denotes the
T23291 44912-44916 NNS denotes mice
T23292 44897-44900 CD denotes two
T23293 44901-44911 JJ denotes transgenic
T23294 44921-44932 RB denotes postnatally
T23295 44933-44939 JJ denotes lethal
T23296 44940-44942 IN denotes as
T23297 44943-44945 IN denotes in
T23298 44946-44949 DT denotes the
T23299 44960-44964 NNS denotes mice
T23300 44950-44952 NN denotes KA
T23301 44953-44959 JJ denotes mutant
T23302 44964-44965 . denotes .
T23303 44965-45099 sentence denotes We did not find any obvious histopathological abnormalities in the internal organs of KA mice that could contribute to the lethality.
T23304 44966-44968 PRP denotes We
T23305 44977-44981 VB denotes find
T23306 44969-44972 VBD denotes did
T23307 44973-44976 RB denotes not
T23308 44982-44985 DT denotes any
T23309 45012-45025 NNS denotes abnormalities
T23310 44986-44993 JJ denotes obvious
T23311 44994-45011 JJ denotes histopathological
T23312 45026-45028 IN denotes in
T23313 45029-45032 DT denotes the
T23314 45042-45048 NNS denotes organs
T23315 45033-45041 JJ denotes internal
T23316 45049-45051 IN denotes of
T23317 45052-45054 NN denotes KA
T23318 45055-45059 NNS denotes mice
T23319 45060-45064 WDT denotes that
T23320 45071-45081 VB denotes contribute
T23321 45065-45070 MD denotes could
T23322 45082-45084 IN denotes to
T23323 45085-45088 DT denotes the
T23324 45089-45098 NN denotes lethality
T23325 45098-45099 . denotes .
T23326 45099-45281 sentence denotes However, the fact that all the mutants had lower weight (Figure 2F) with hardly any evidence of solid food in their stomach indicates that the mutants might have died of starvation.
T23327 45100-45107 RB denotes However
T23328 45224-45233 VBZ denotes indicates
T23329 45107-45109 , denotes ,
T23330 45109-45112 DT denotes the
T23331 45113-45117 NN denotes fact
T23332 45118-45122 IN denotes that
T23333 45139-45142 VBD denotes had
T23334 45123-45126 PDT denotes all
T23335 45131-45138 NNS denotes mutants
T23336 45127-45130 DT denotes the
T23337 45143-45148 JJR denotes lower
T23338 45149-45155 NN denotes weight
T23339 45156-45157 -LRB- denotes (
T23340 45164-45166 NN denotes 2F
T23341 45157-45163 NN denotes Figure
T23342 45166-45167 -RRB- denotes )
T23343 45168-45172 IN denotes with
T23344 45173-45179 RB denotes hardly
T23345 45184-45192 NN denotes evidence
T23346 45180-45183 DT denotes any
T23347 45193-45195 IN denotes of
T23348 45196-45201 JJ denotes solid
T23349 45202-45206 NN denotes food
T23350 45207-45209 IN denotes in
T23351 45210-45215 PRP$ denotes their
T23352 45216-45223 NN denotes stomach
T23353 45234-45238 IN denotes that
T23354 45262-45266 VBN denotes died
T23355 45239-45242 DT denotes the
T23356 45243-45250 NNS denotes mutants
T23357 45251-45256 MD denotes might
T23358 45257-45261 VB denotes have
T23359 45267-45269 IN denotes of
T23360 45270-45280 NN denotes starvation
T23361 45280-45281 . denotes .
T23362 45281-45400 sentence denotes Dermal fat was reduced in the mutant skin, possibly as a consequence of poor nutrition caused by the absence of teeth.
T23363 45282-45288 JJ denotes Dermal
T23364 45289-45292 NN denotes fat
T23365 45297-45304 VBN denotes reduced
T23366 45293-45296 VBD denotes was
T23367 45305-45307 IN denotes in
T23368 45308-45311 DT denotes the
T23369 45319-45323 NN denotes skin
T23370 45312-45318 JJ denotes mutant
T23371 45323-45325 , denotes ,
T23372 45325-45333 RB denotes possibly
T23373 45334-45336 IN denotes as
T23374 45337-45338 DT denotes a
T23375 45339-45350 NN denotes consequence
T23376 45351-45353 IN denotes of
T23377 45354-45358 JJ denotes poor
T23378 45359-45368 NN denotes nutrition
T23379 45369-45375 VBN denotes caused
T23380 45376-45378 IN denotes by
T23381 45379-45382 DT denotes the
T23382 45383-45390 NN denotes absence
T23383 45391-45393 IN denotes of
T23384 45394-45399 NNS denotes teeth
T23385 45399-45400 . denotes .
T23386 45400-45613 sentence denotes Since the weight loss in KA mutants started from P8–P10 while pups were still nursed by their mothers, starvation due to lack of teeth cannot be the sole cause of death, but is likely to be a contributing factor.
T23387 45401-45406 IN denotes Since
T23388 45437-45444 VBN denotes started
T23389 45407-45410 DT denotes the
T23390 45418-45422 NN denotes loss
T23391 45411-45417 NN denotes weight
T23392 45423-45425 IN denotes in
T23393 45426-45428 NN denotes KA
T23394 45429-45436 NNS denotes mutants
T23395 45543-45545 VB denotes be
T23396 45445-45449 IN denotes from
T23397 45450-45452 NN denotes P8
T23398 45452-45453 SYM denotes
T23399 45453-45456 NN denotes P10
T23400 45457-45462 IN denotes while
T23401 45479-45485 VBN denotes nursed
T23402 45463-45467 NNS denotes pups
T23403 45468-45472 VBD denotes were
T23404 45473-45478 RB denotes still
T23405 45486-45488 IN denotes by
T23406 45489-45494 PRP$ denotes their
T23407 45495-45502 NNS denotes mothers
T23408 45502-45504 , denotes ,
T23409 45504-45514 NN denotes starvation
T23410 45515-45518 IN denotes due
T23411 45519-45521 IN denotes to
T23412 45522-45526 NN denotes lack
T23413 45527-45529 IN denotes of
T23414 45530-45535 NNS denotes teeth
T23415 45536-45539 MD denotes can
T23416 45539-45542 RB denotes not
T23417 45546-45549 DT denotes the
T23418 45555-45560 NN denotes cause
T23419 45550-45554 JJ denotes sole
T23420 45561-45563 IN denotes of
T23421 45564-45569 NN denotes death
T23422 45569-45571 , denotes ,
T23423 45571-45574 CC denotes but
T23424 45575-45577 VBZ denotes is
T23425 45578-45584 JJ denotes likely
T23426 45585-45587 TO denotes to
T23427 45588-45590 VB denotes be
T23428 45591-45592 DT denotes a
T23429 45606-45612 NN denotes factor
T23430 45593-45605 VBG denotes contributing
T23431 45612-45613 . denotes .
T23432 45613-45810 sentence denotes Absence of teeth and mammary glands have been observed in mice deficient in Lef1 and ectopically expressing Dkk1 [29,30] but their absence was due to the block in development before the bud stage.
T23433 45614-45621 NN denotes Absence
T23434 45660-45668 VBN denotes observed
T23435 45622-45624 IN denotes of
T23436 45625-45630 NNS denotes teeth
T23437 45631-45634 CC denotes and
T23438 45635-45642 JJ denotes mammary
T23439 45643-45649 NNS denotes glands
T23440 45650-45654 VBP denotes have
T23441 45655-45659 VBN denotes been
T23442 45669-45671 IN denotes in
T23443 45672-45676 NNS denotes mice
T23444 45677-45686 JJ denotes deficient
T23445 45687-45689 IN denotes in
T23446 45690-45694 NN denotes Lef1
T23447 45695-45698 CC denotes and
T23448 45699-45710 RB denotes ectopically
T23449 45711-45721 VBG denotes expressing
T23450 45722-45726 NN denotes Dkk1
T23451 45727-45728 -LRB- denotes [
T23452 45731-45733 CD denotes 30
T23453 45728-45730 CD denotes 29
T23454 45730-45731 , denotes ,
T23455 45733-45734 -RRB- denotes ]
T23456 45735-45738 CC denotes but
T23457 45739-45744 PRP$ denotes their
T23458 45745-45752 NN denotes absence
T23459 45753-45756 VBD denotes was
T23460 45757-45760 IN denotes due
T23461 45761-45763 IN denotes to
T23462 45764-45767 DT denotes the
T23463 45768-45773 NN denotes block
T23464 45774-45776 IN denotes in
T23465 45777-45788 NN denotes development
T23466 45789-45795 IN denotes before
T23467 45796-45799 DT denotes the
T23468 45804-45809 NN denotes stage
T23469 45800-45803 NN denotes bud
T23470 45809-45810 . denotes .
T23471 45810-45948 sentence denotes Hence, neither loss nor excess of tooth bud formation allows proper development of teeth for mice to have a healthy diet and normal life.
T23472 45811-45816 RB denotes Hence
T23473 45865-45871 VBZ denotes allows
T23474 45816-45818 , denotes ,
T23475 45818-45825 CC denotes neither
T23476 45826-45830 NN denotes loss
T23477 45831-45834 CC denotes nor
T23478 45835-45841 NN denotes excess
T23479 45842-45844 IN denotes of
T23480 45845-45850 JJ denotes tooth
T23481 45851-45854 NN denotes bud
T23482 45855-45864 NN denotes formation
T23483 45872-45878 JJ denotes proper
T23484 45879-45890 NN denotes development
T23485 45891-45893 IN denotes of
T23486 45894-45899 NNS denotes teeth
T23487 45900-45903 IN denotes for
T23488 45912-45916 VB denotes have
T23489 45904-45908 NNS denotes mice
T23490 45909-45911 TO denotes to
T23491 45917-45918 DT denotes a
T23492 45927-45931 NN denotes diet
T23493 45919-45926 JJ denotes healthy
T23494 45932-45935 CC denotes and
T23495 45936-45942 JJ denotes normal
T23496 45943-45947 NN denotes life
T23497 45947-45948 . denotes .
T23498 45948-46074 sentence denotes Mechanistic studies to understand how increased levels of β-catenin leads to altered skin and tooth phenotypes are under way.
T23499 45949-45960 JJ denotes Mechanistic
T23500 45961-45968 NNS denotes studies
T23501 46060-46063 VBP denotes are
T23502 45969-45971 TO denotes to
T23503 45972-45982 VB denotes understand
T23504 45983-45986 WRB denotes how
T23505 46017-46022 VBZ denotes leads
T23506 45987-45996 VBN denotes increased
T23507 45997-46003 NNS denotes levels
T23508 46004-46006 IN denotes of
T23509 46007-46008 NN denotes β
T23510 46009-46016 NN denotes catenin
T23511 46008-46009 HYPH denotes -
T23512 46023-46025 IN denotes to
T23513 46026-46033 JJ denotes altered
T23514 46049-46059 NNS denotes phenotypes
T23515 46034-46038 NN denotes skin
T23516 46039-46042 CC denotes and
T23517 46043-46048 NN denotes tooth
T23518 46064-46069 IN denotes under
T23519 46070-46073 NN denotes way
T23520 46073-46074 . denotes .
T25417 46076-46079 NN denotes Apc
T25418 46080-46083 CC denotes and
T25419 46084-46090 NN denotes Thymus
T25420 46091-46104 NN denotes Organogenesis
T25421 46104-46360 sentence denotes In this study, we observed that K14-driven loss of Apc resulted in a small thymus with severe squamous metaplasia leading to the formation of numerous pyogranuloma and loss of proper meshwork structure for thymocyte maturation, rendering the mice athymic.
T25422 46105-46107 IN denotes In
T25423 46123-46131 VBD denotes observed
T25424 46108-46112 DT denotes this
T25425 46113-46118 NN denotes study
T25426 46118-46120 , denotes ,
T25427 46120-46122 PRP denotes we
T25428 46132-46136 IN denotes that
T25429 46160-46168 VBD denotes resulted
T25430 46137-46140 NN denotes K14
T25431 46141-46147 VBN denotes driven
T25432 46140-46141 HYPH denotes -
T25433 46148-46152 NN denotes loss
T25434 46153-46155 IN denotes of
T25435 46156-46159 NN denotes Apc
T25436 46169-46171 IN denotes in
T25437 46172-46173 DT denotes a
T25438 46180-46186 NN denotes thymus
T25439 46174-46179 JJ denotes small
T25440 46187-46191 IN denotes with
T25441 46192-46198 JJ denotes severe
T25442 46208-46218 NN denotes metaplasia
T25443 46199-46207 JJ denotes squamous
T25444 46219-46226 VBG denotes leading
T25445 46227-46229 IN denotes to
T25446 46230-46233 DT denotes the
T25447 46234-46243 NN denotes formation
T25448 46244-46246 IN denotes of
T25449 46247-46255 JJ denotes numerous
T25450 46256-46268 NN denotes pyogranuloma
T25451 46269-46272 CC denotes and
T25452 46273-46277 NN denotes loss
T25453 46278-46280 IN denotes of
T25454 46281-46287 JJ denotes proper
T25455 46297-46306 NN denotes structure
T25456 46288-46296 NN denotes meshwork
T25457 46307-46310 IN denotes for
T25458 46311-46320 NN denotes thymocyte
T25459 46321-46331 NN denotes maturation
T25460 46331-46333 , denotes ,
T25461 46333-46342 VBG denotes rendering
T25462 46343-46346 DT denotes the
T25463 46347-46351 NNS denotes mice
T25464 46352-46359 JJ denotes athymic
T25465 46359-46360 . denotes .
T25466 46360-46578 sentence denotes Previous studies have shown that in normal adult thymus K14 expression is found together with K5 in the stellate medullary TECs, but not in association with K5+ TECs in the cortex or at the cortico-medullary junction.
T25467 46361-46369 JJ denotes Previous
T25468 46370-46377 NNS denotes studies
T25469 46383-46388 VBN denotes shown
T25470 46378-46382 VBP denotes have
T25471 46389-46393 IN denotes that
T25472 46435-46440 VBN denotes found
T25473 46394-46396 IN denotes in
T25474 46397-46403 JJ denotes normal
T25475 46410-46416 NN denotes thymus
T25476 46404-46409 JJ denotes adult
T25477 46417-46420 NN denotes K14
T25478 46421-46431 NN denotes expression
T25479 46432-46434 VBZ denotes is
T25480 46441-46449 RB denotes together
T25481 46498-46500 IN denotes in
T25482 46450-46454 IN denotes with
T25483 46455-46457 NN denotes K5
T25484 46458-46460 IN denotes in
T25485 46461-46464 DT denotes the
T25486 46484-46488 NNS denotes TECs
T25487 46465-46473 JJ denotes stellate
T25488 46474-46483 JJ denotes medullary
T25489 46488-46490 , denotes ,
T25490 46490-46493 CC denotes but
T25491 46494-46497 RB denotes not
T25492 46501-46512 NN denotes association
T25493 46513-46517 IN denotes with
T25494 46518-46520 NN denotes K5
T25495 46522-46526 NNS denotes TECs
T25496 46520-46521 SYM denotes +
T25497 46527-46529 IN denotes in
T25498 46530-46533 DT denotes the
T25499 46534-46540 NN denotes cortex
T25500 46541-46543 CC denotes or
T25501 46544-46546 IN denotes at
T25502 46547-46550 DT denotes the
T25503 46569-46577 NN denotes junction
T25504 46551-46558 JJ denotes cortico
T25505 46559-46568 JJ denotes medullary
T25506 46558-46559 HYPH denotes -
T25507 46577-46578 . denotes .
T25508 46578-46770 sentence denotes In addition, it has been demonstrated that K14+ TECs do not coexpress K8; hence, there are two distinct medullary subsets, namely a K8−K14+ stellate subset and a K8+K14− globular subset [32].
T25509 46579-46581 IN denotes In
T25510 46604-46616 VBN denotes demonstrated
T25511 46582-46590 NN denotes addition
T25512 46590-46592 , denotes ,
T25513 46592-46594 PRP denotes it
T25514 46595-46598 VBZ denotes has
T25515 46599-46603 VBN denotes been
T25516 46666-46669 VBP denotes are
T25517 46617-46621 IN denotes that
T25518 46639-46648 VB denotes coexpress
T25519 46622-46625 NN denotes K14
T25520 46627-46631 NNS denotes TECs
T25521 46625-46626 SYM denotes +
T25522 46632-46634 VBP denotes do
T25523 46635-46638 RB denotes not
T25524 46649-46651 NN denotes K8
T25525 46651-46652 : denotes ;
T25526 46653-46658 RB denotes hence
T25527 46658-46660 , denotes ,
T25528 46660-46665 EX denotes there
T25529 46670-46673 CD denotes two
T25530 46693-46700 NNS denotes subsets
T25531 46674-46682 JJ denotes distinct
T25532 46683-46692 JJ denotes medullary
T25533 46700-46702 , denotes ,
T25534 46702-46708 RB denotes namely
T25535 46728-46734 NN denotes subset
T25536 46709-46710 DT denotes a
T25537 46711-46713 NN denotes K8
T25538 46713-46714 HYPH denotes
T25539 46714-46717 NN denotes K14
T25540 46717-46718 SYM denotes +
T25541 46719-46727 JJ denotes stellate
T25542 46735-46738 CC denotes and
T25543 46739-46740 DT denotes a
T25544 46758-46764 NN denotes subset
T25545 46741-46743 NN denotes K8
T25546 46743-46744 SYM denotes +
T25547 46744-46747 NN denotes K14
T25548 46747-46748 SYM denotes
T25549 46749-46757 JJ denotes globular
T25550 46765-46766 -LRB- denotes [
T25551 46766-46768 CD denotes 32
T25552 46768-46769 -RRB- denotes ]
T25553 46769-46770 . denotes .
T25554 46770-46972 sentence denotes In agreement with the previous results, in P3 normal thymus K14 expression was restricted to stellate medullary TECs (Figure 6D), whereas K8 expression was found throughout the TECs (unpublished data).
T25555 46771-46773 IN denotes In
T25556 46850-46860 VBN denotes restricted
T25557 46774-46783 NN denotes agreement
T25558 46784-46788 IN denotes with
T25559 46789-46792 DT denotes the
T25560 46802-46809 NNS denotes results
T25561 46793-46801 JJ denotes previous
T25562 46809-46811 , denotes ,
T25563 46811-46813 IN denotes in
T25564 46814-46816 NN denotes P3
T25565 46824-46830 NN denotes thymus
T25566 46817-46823 JJ denotes normal
T25567 46831-46834 NN denotes K14
T25568 46835-46845 NN denotes expression
T25569 46846-46849 VBD denotes was
T25570 46861-46863 IN denotes to
T25571 46864-46872 JJ denotes stellate
T25572 46883-46887 NNS denotes TECs
T25573 46873-46882 JJ denotes medullary
T25574 46888-46889 -LRB- denotes (
T25575 46896-46898 NN denotes 6D
T25576 46889-46895 NN denotes Figure
T25577 46898-46899 -RRB- denotes )
T25578 46899-46901 , denotes ,
T25579 46901-46908 IN denotes whereas
T25580 46927-46932 VBN denotes found
T25581 46909-46911 NN denotes K8
T25582 46912-46922 NN denotes expression
T25583 46923-46926 VBD denotes was
T25584 46933-46943 IN denotes throughout
T25585 46944-46947 DT denotes the
T25586 46948-46952 NNS denotes TECs
T25587 46953-46954 -LRB- denotes (
T25588 46966-46970 NNS denotes data
T25589 46954-46965 JJ denotes unpublished
T25590 46970-46971 -RRB- denotes )
T25591 46971-46972 . denotes .
T25592 46972-47079 sentence denotes We could not clarify whether these two keratins were coexpressed in the same TECs without double-staining.
T25593 46973-46975 PRP denotes We
T25594 46986-46993 VB denotes clarify
T25595 46976-46981 MD denotes could
T25596 46982-46985 RB denotes not
T25597 46994-47001 IN denotes whether
T25598 47026-47037 VBN denotes coexpressed
T25599 47002-47007 DT denotes these
T25600 47012-47020 NNS denotes keratins
T25601 47008-47011 CD denotes two
T25602 47021-47025 VBD denotes were
T25603 47038-47040 IN denotes in
T25604 47041-47044 DT denotes the
T25605 47050-47054 NNS denotes TECs
T25606 47045-47049 JJ denotes same
T25607 47055-47062 IN denotes without
T25608 47063-47069 NN denotes double
T25609 47070-47078 NN denotes staining
T25610 47069-47070 HYPH denotes -
T25611 47078-47079 . denotes .
T25612 47079-47367 sentence denotes There were individual differences among mutants and these were prominently reflected in the histological abnormalities of the thymus at P3, but as the older surviving mutants all showed the same histopathologies of the thymus, the mutant thymi eventually seem to result in the same fate.
T25613 47080-47085 EX denotes There
T25614 47086-47090 VBD denotes were
T25615 47091-47101 JJ denotes individual
T25616 47102-47113 NNS denotes differences
T25617 47114-47119 IN denotes among
T25618 47120-47127 NNS denotes mutants
T25619 47128-47131 CC denotes and
T25620 47132-47137 DT denotes these
T25621 47155-47164 VBN denotes reflected
T25622 47138-47142 VBD denotes were
T25623 47143-47154 RB denotes prominently
T25624 47165-47167 IN denotes in
T25625 47168-47171 DT denotes the
T25626 47185-47198 NNS denotes abnormalities
T25627 47172-47184 JJ denotes histological
T25628 47199-47201 IN denotes of
T25629 47202-47205 DT denotes the
T25630 47206-47212 NN denotes thymus
T25631 47213-47215 IN denotes at
T25632 47216-47218 NN denotes P3
T25633 47218-47220 , denotes ,
T25634 47220-47223 CC denotes but
T25635 47224-47226 IN denotes as
T25636 47259-47265 VBD denotes showed
T25637 47227-47230 DT denotes the
T25638 47247-47254 NNS denotes mutants
T25639 47231-47236 JJR denotes older
T25640 47237-47246 VBG denotes surviving
T25641 47255-47258 DT denotes all
T25642 47335-47339 VBP denotes seem
T25643 47266-47269 DT denotes the
T25644 47275-47291 NNS denotes histopathologies
T25645 47270-47274 JJ denotes same
T25646 47292-47294 IN denotes of
T25647 47295-47298 DT denotes the
T25648 47299-47305 NN denotes thymus
T25649 47305-47307 , denotes ,
T25650 47307-47310 DT denotes the
T25651 47318-47323 NNS denotes thymi
T25652 47311-47317 JJ denotes mutant
T25653 47324-47334 RB denotes eventually
T25654 47340-47342 TO denotes to
T25655 47343-47349 VB denotes result
T25656 47350-47352 IN denotes in
T25657 47353-47356 DT denotes the
T25658 47362-47366 NN denotes fate
T25659 47357-47361 JJ denotes same
T25660 47366-47367 . denotes .
T25661 47367-47837 sentence denotes It is unclear when K14-cre induction actually takes place in the mutant thymus, but as the population of cells showing a strong nuclear β-catenin staining as well as the cells expressing K14 were small and thymic epithelial compartments still existed in a mild P3 mutant thymus (Figure 6E and 6F), it seems that initial differentiation to medullary and cortical TECs and thymocyte colonization have already taken place prior to the major effects of K14-driven Apc loss.
T25662 47368-47370 PRP denotes It
T25663 47371-47373 VBZ denotes is
T25664 47374-47381 JJ denotes unclear
T25665 47382-47386 WRB denotes when
T25666 47414-47419 VBZ denotes takes
T25667 47387-47390 NN denotes K14
T25668 47391-47394 NN denotes cre
T25669 47390-47391 HYPH denotes -
T25670 47395-47404 NN denotes induction
T25671 47405-47413 RB denotes actually
T25672 47420-47425 NN denotes place
T25673 47426-47428 IN denotes in
T25674 47429-47432 DT denotes the
T25675 47440-47446 NN denotes thymus
T25676 47433-47439 JJ denotes mutant
T25677 47446-47448 , denotes ,
T25678 47448-47451 CC denotes but
T25679 47452-47454 IN denotes as
T25680 47559-47563 VBD denotes were
T25681 47455-47458 DT denotes the
T25682 47459-47469 NN denotes population
T25683 47470-47472 IN denotes of
T25684 47473-47478 NNS denotes cells
T25685 47479-47486 VBG denotes showing
T25686 47487-47488 DT denotes a
T25687 47514-47522 NN denotes staining
T25688 47489-47495 JJ denotes strong
T25689 47496-47503 JJ denotes nuclear
T25690 47504-47505 NN denotes β
T25691 47506-47513 NN denotes catenin
T25692 47505-47506 HYPH denotes -
T25693 47523-47525 RB denotes as
T25694 47531-47533 IN denotes as
T25695 47526-47530 RB denotes well
T25696 47534-47537 DT denotes the
T25697 47538-47543 NNS denotes cells
T25698 47544-47554 VBG denotes expressing
T25699 47555-47558 NN denotes K14
T25700 47669-47674 VBZ denotes seems
T25701 47564-47569 JJ denotes small
T25702 47570-47573 CC denotes and
T25703 47574-47580 JJ denotes thymic
T25704 47592-47604 NNS denotes compartments
T25705 47581-47591 JJ denotes epithelial
T25706 47611-47618 VBD denotes existed
T25707 47605-47610 RB denotes still
T25708 47619-47621 IN denotes in
T25709 47622-47623 DT denotes a
T25710 47639-47645 NN denotes thymus
T25711 47624-47628 JJ denotes mild
T25712 47629-47631 NN denotes P3
T25713 47632-47638 JJ denotes mutant
T25714 47646-47647 -LRB- denotes (
T25715 47654-47656 NN denotes 6E
T25716 47647-47653 NN denotes Figure
T25717 47657-47660 CC denotes and
T25718 47661-47663 NN denotes 6F
T25719 47663-47664 -RRB- denotes )
T25720 47664-47666 , denotes ,
T25721 47666-47668 PRP denotes it
T25722 47675-47679 IN denotes that
T25723 47775-47780 VBN denotes taken
T25724 47680-47687 JJ denotes initial
T25725 47688-47703 NN denotes differentiation
T25726 47704-47706 IN denotes to
T25727 47707-47716 JJ denotes medullary
T25728 47730-47734 NNS denotes TECs
T25729 47717-47720 CC denotes and
T25730 47721-47729 JJ denotes cortical
T25731 47735-47738 CC denotes and
T25732 47739-47748 NN denotes thymocyte
T25733 47749-47761 NN denotes colonization
T25734 47762-47766 VBP denotes have
T25735 47767-47774 RB denotes already
T25736 47781-47786 NN denotes place
T25737 47787-47792 JJ denotes prior
T25738 47793-47795 IN denotes to
T25739 47796-47799 DT denotes the
T25740 47806-47813 NNS denotes effects
T25741 47800-47805 JJ denotes major
T25742 47814-47816 IN denotes of
T25743 47817-47820 NN denotes K14
T25744 47821-47827 VBN denotes driven
T25745 47820-47821 HYPH denotes -
T25746 47832-47836 NN denotes loss
T25747 47828-47831 NN denotes Apc
T25748 47836-47837 . denotes .
T25749 47837-48040 sentence denotes However, cells with nuclear β-catenin and K8+K14+ double-positive epithelial cells increased subsequently, associated with active proliferation in the latter group of cells and loss of TEC compartments.
T25750 47838-47845 RB denotes However
T25751 47921-47930 VBD denotes increased
T25752 47845-47847 , denotes ,
T25753 47847-47852 NNS denotes cells
T25754 47853-47857 IN denotes with
T25755 47858-47865 JJ denotes nuclear
T25756 47868-47875 NN denotes catenin
T25757 47866-47867 NN denotes β
T25758 47867-47868 HYPH denotes -
T25759 47915-47920 NNS denotes cells
T25760 47876-47879 CC denotes and
T25761 47880-47882 NN denotes K8
T25762 47895-47903 JJ denotes positive
T25763 47882-47883 SYM denotes +
T25764 47883-47886 NN denotes K14
T25765 47886-47887 SYM denotes +
T25766 47888-47894 JJ denotes double
T25767 47894-47895 HYPH denotes -
T25768 47904-47914 JJ denotes epithelial
T25769 47931-47943 RB denotes subsequently
T25770 47943-47945 , denotes ,
T25771 47945-47955 JJ denotes associated
T25772 47956-47960 IN denotes with
T25773 47961-47967 JJ denotes active
T25774 47968-47981 NN denotes proliferation
T25775 47982-47984 IN denotes in
T25776 47985-47988 DT denotes the
T25777 47996-48001 NN denotes group
T25778 47989-47995 JJ denotes latter
T25779 48002-48004 IN denotes of
T25780 48005-48010 NNS denotes cells
T25781 48011-48014 CC denotes and
T25782 48015-48019 NN denotes loss
T25783 48020-48022 IN denotes of
T25784 48023-48026 NN denotes TEC
T25785 48027-48039 NNS denotes compartments
T25786 48039-48040 . denotes .
T25787 48040-48331 sentence denotes With age, β-catenin expression pattern became more diffuse and fewer epithelial cells showed nuclear localization but K8+K14+ cells remained, forming concentric structures of epithelial cells filled with hard keratin deposits and infiltrated with vast number of neutrophils and macrophages.
T25788 48041-48045 IN denotes With
T25789 48080-48086 VBD denotes became
T25790 48046-48049 NN denotes age
T25791 48049-48051 , denotes ,
T25792 48051-48052 NN denotes β
T25793 48053-48060 NN denotes catenin
T25794 48052-48053 HYPH denotes -
T25795 48072-48079 NN denotes pattern
T25796 48061-48071 NN denotes expression
T25797 48087-48091 RBR denotes more
T25798 48092-48099 JJ denotes diffuse
T25799 48100-48103 CC denotes and
T25800 48104-48109 JJR denotes fewer
T25801 48121-48126 NNS denotes cells
T25802 48110-48120 JJ denotes epithelial
T25803 48127-48133 VBD denotes showed
T25804 48134-48141 JJ denotes nuclear
T25805 48142-48154 NN denotes localization
T25806 48155-48158 CC denotes but
T25807 48159-48161 NN denotes K8
T25808 48167-48172 NNS denotes cells
T25809 48161-48162 SYM denotes +
T25810 48162-48165 NN denotes K14
T25811 48165-48166 SYM denotes +
T25812 48173-48181 VBD denotes remained
T25813 48181-48183 , denotes ,
T25814 48183-48190 VBG denotes forming
T25815 48191-48201 JJ denotes concentric
T25816 48202-48212 NNS denotes structures
T25817 48213-48215 IN denotes of
T25818 48216-48226 JJ denotes epithelial
T25819 48227-48232 NNS denotes cells
T25820 48233-48239 VBN denotes filled
T25821 48240-48244 IN denotes with
T25822 48245-48249 JJ denotes hard
T25823 48258-48266 NNS denotes deposits
T25824 48250-48257 NN denotes keratin
T25825 48267-48270 CC denotes and
T25826 48271-48282 VBN denotes infiltrated
T25827 48283-48287 IN denotes with
T25828 48288-48292 JJ denotes vast
T25829 48293-48299 NN denotes number
T25830 48300-48302 IN denotes of
T25831 48303-48314 NNS denotes neutrophils
T25832 48315-48318 CC denotes and
T25833 48319-48330 NNS denotes macrophages
T25834 48330-48331 . denotes .
T25835 48331-48426 sentence denotes Only a few epithelial cells were dividing and hardly any thymocytes were present by this time.
T25836 48332-48336 RB denotes Only
T25837 48354-48359 NNS denotes cells
T25838 48337-48338 DT denotes a
T25839 48339-48342 JJ denotes few
T25840 48343-48353 JJ denotes epithelial
T25841 48365-48373 VBG denotes dividing
T25842 48360-48364 VBD denotes were
T25843 48374-48377 CC denotes and
T25844 48378-48384 RB denotes hardly
T25845 48389-48399 NNS denotes thymocytes
T25846 48385-48388 DT denotes any
T25847 48400-48404 VBD denotes were
T25848 48405-48412 JJ denotes present
T25849 48413-48415 IN denotes by
T25850 48416-48420 DT denotes this
T25851 48421-48425 NN denotes time
T25852 48425-48426 . denotes .
T25853 48426-48711 sentence denotes These results suggest that with the deletion of Apc in TECs, stabililization and nuclear localization of β-catenin took place and subsequently these cells differentiated into keratinocytes that expressed both K14 and K8, similar to the basal cells of the skin, instead of TEC subsets.
T25854 48427-48432 DT denotes These
T25855 48433-48440 NNS denotes results
T25856 48441-48448 VBP denotes suggest
T25857 48449-48453 IN denotes that
T25858 48542-48546 VBD denotes took
T25859 48454-48458 IN denotes with
T25860 48459-48462 DT denotes the
T25861 48463-48471 NN denotes deletion
T25862 48472-48474 IN denotes of
T25863 48475-48478 NN denotes Apc
T25864 48479-48481 IN denotes in
T25865 48482-48486 NNS denotes TECs
T25866 48486-48488 , denotes ,
T25867 48488-48503 NN denotes stabililization
T25868 48504-48507 CC denotes and
T25869 48508-48515 JJ denotes nuclear
T25870 48516-48528 NN denotes localization
T25871 48529-48531 IN denotes of
T25872 48532-48533 NN denotes β
T25873 48534-48541 NN denotes catenin
T25874 48533-48534 HYPH denotes -
T25875 48547-48552 NN denotes place
T25876 48553-48556 CC denotes and
T25877 48557-48569 RB denotes subsequently
T25878 48582-48596 VBD denotes differentiated
T25879 48570-48575 DT denotes these
T25880 48576-48581 NNS denotes cells
T25881 48597-48601 IN denotes into
T25882 48602-48615 NNS denotes keratinocytes
T25883 48616-48620 WDT denotes that
T25884 48621-48630 VBD denotes expressed
T25885 48631-48635 CC denotes both
T25886 48636-48639 NN denotes K14
T25887 48640-48643 CC denotes and
T25888 48644-48646 NN denotes K8
T25889 48646-48648 , denotes ,
T25890 48648-48655 JJ denotes similar
T25891 48656-48658 IN denotes to
T25892 48659-48662 DT denotes the
T25893 48669-48674 NNS denotes cells
T25894 48663-48668 JJ denotes basal
T25895 48675-48677 IN denotes of
T25896 48678-48681 DT denotes the
T25897 48682-48686 NN denotes skin
T25898 48686-48688 , denotes ,
T25899 48688-48695 RB denotes instead
T25900 48696-48698 IN denotes of
T25901 48699-48702 NN denotes TEC
T25902 48703-48710 NNS denotes subsets
T25903 48710-48711 . denotes .
T25904 48711-48969 sentence denotes The expansion and differentiation of these keratinocytes lead to loss of proper thymic epithelial compartments and in turn produced and deposited the hard keratins that consequently caused vast amount of neutrophils and macrophages to infiltrate the thymus.
T25905 48712-48715 DT denotes The
T25906 48716-48725 NN denotes expansion
T25907 48769-48773 VBP denotes lead
T25908 48726-48729 CC denotes and
T25909 48730-48745 NN denotes differentiation
T25910 48746-48748 IN denotes of
T25911 48749-48754 DT denotes these
T25912 48755-48768 NNS denotes keratinocytes
T25913 48774-48776 IN denotes to
T25914 48777-48781 NN denotes loss
T25915 48782-48784 IN denotes of
T25916 48785-48791 JJ denotes proper
T25917 48810-48822 NNS denotes compartments
T25918 48792-48798 JJ denotes thymic
T25919 48799-48809 JJ denotes epithelial
T25920 48823-48826 CC denotes and
T25921 48827-48829 IN denotes in
T25922 48835-48843 VBD denotes produced
T25923 48830-48834 NN denotes turn
T25924 48844-48847 CC denotes and
T25925 48848-48857 VBD denotes deposited
T25926 48858-48861 DT denotes the
T25927 48867-48875 NNS denotes keratins
T25928 48862-48866 JJ denotes hard
T25929 48876-48880 WDT denotes that
T25930 48894-48900 VBD denotes caused
T25931 48881-48893 RB denotes consequently
T25932 48901-48905 JJ denotes vast
T25933 48906-48912 NN denotes amount
T25934 48947-48957 VB denotes infiltrate
T25935 48913-48915 IN denotes of
T25936 48916-48927 NNS denotes neutrophils
T25937 48928-48931 CC denotes and
T25938 48932-48943 NNS denotes macrophages
T25939 48944-48946 TO denotes to
T25940 48958-48961 DT denotes the
T25941 48962-48968 NN denotes thymus
T25942 48968-48969 . denotes .
T25943 48969-49097 sentence denotes These aberrant epithelial structures eventually have overtaken the whole of the thymus and driven out the colonized thymocytes.
T25944 48970-48975 DT denotes These
T25945 48996-49006 NNS denotes structures
T25946 48976-48984 JJ denotes aberrant
T25947 48985-48995 JJ denotes epithelial
T25948 49023-49032 VBN denotes overtaken
T25949 49007-49017 RB denotes eventually
T25950 49018-49022 VBP denotes have
T25951 49033-49036 DT denotes the
T25952 49037-49042 NN denotes whole
T25953 49043-49045 IN denotes of
T25954 49046-49049 DT denotes the
T25955 49050-49056 NN denotes thymus
T25956 49057-49060 CC denotes and
T25957 49061-49067 VBN denotes driven
T25958 49068-49071 RP denotes out
T25959 49072-49075 DT denotes the
T25960 49086-49096 NNS denotes thymocytes
T25961 49076-49085 VBN denotes colonized
T25962 49096-49097 . denotes .
T25963 49097-49370 sentence denotes K14-driven loss of Apc and subsequent constitutive expression of β-catenin in TECs have therefore misdirected them to wrong epithelial cell fate, not allowing proper differentiation to either cortical or medullary TECs, which is essential for normal thymocyte development.
T25964 49098-49101 NN denotes K14
T25965 49102-49108 VBN denotes driven
T25966 49101-49102 HYPH denotes -
T25967 49109-49113 NN denotes loss
T25968 49196-49207 VBN denotes misdirected
T25969 49114-49116 IN denotes of
T25970 49117-49120 NN denotes Apc
T25971 49121-49124 CC denotes and
T25972 49125-49135 JJ denotes subsequent
T25973 49149-49159 NN denotes expression
T25974 49136-49148 JJ denotes constitutive
T25975 49160-49162 IN denotes of
T25976 49163-49164 NN denotes β
T25977 49165-49172 NN denotes catenin
T25978 49164-49165 HYPH denotes -
T25979 49173-49175 IN denotes in
T25980 49176-49180 NNS denotes TECs
T25981 49181-49185 VBP denotes have
T25982 49186-49195 RB denotes therefore
T25983 49208-49212 PRP denotes them
T25984 49213-49215 IN denotes to
T25985 49216-49221 JJ denotes wrong
T25986 49238-49242 NN denotes fate
T25987 49222-49232 JJ denotes epithelial
T25988 49233-49237 NN denotes cell
T25989 49242-49244 , denotes ,
T25990 49244-49247 RB denotes not
T25991 49248-49256 VBG denotes allowing
T25992 49257-49263 JJ denotes proper
T25993 49264-49279 NN denotes differentiation
T25994 49280-49282 IN denotes to
T25995 49283-49289 CC denotes either
T25996 49290-49298 JJ denotes cortical
T25997 49312-49316 NNS denotes TECs
T25998 49299-49301 CC denotes or
T25999 49302-49311 JJ denotes medullary
T26000 49316-49318 , denotes ,
T26001 49318-49323 WDT denotes which
T26002 49324-49326 VBZ denotes is
T26003 49327-49336 JJ denotes essential
T26004 49337-49340 IN denotes for
T26005 49341-49347 JJ denotes normal
T26006 49358-49369 NN denotes development
T26007 49348-49357 NN denotes thymocyte
T26008 49369-49370 . denotes .
T26009 49370-49563 sentence denotes This is not only evident from the lack of dividing thymocytes in the mutant thymus by P13, but also by the differential expression pattern of keratins, which were more skin-like than TEC-like.
T26010 49371-49375 DT denotes This
T26011 49376-49378 VBZ denotes is
T26012 49379-49382 RB denotes not
T26013 49383-49387 RB denotes only
T26014 49388-49395 JJ denotes evident
T26015 49396-49400 IN denotes from
T26016 49401-49404 DT denotes the
T26017 49405-49409 NN denotes lack
T26018 49410-49412 IN denotes of
T26019 49413-49421 VBG denotes dividing
T26020 49422-49432 NNS denotes thymocytes
T26021 49433-49435 IN denotes in
T26022 49436-49439 DT denotes the
T26023 49447-49453 NN denotes thymus
T26024 49440-49446 JJ denotes mutant
T26025 49454-49456 IN denotes by
T26026 49457-49460 NN denotes P13
T26027 49460-49462 , denotes ,
T26028 49462-49465 CC denotes but
T26029 49466-49470 RB denotes also
T26030 49471-49473 IN denotes by
T26031 49474-49477 DT denotes the
T26032 49502-49509 NN denotes pattern
T26033 49478-49490 JJ denotes differential
T26034 49491-49501 NN denotes expression
T26035 49510-49512 IN denotes of
T26036 49513-49521 NNS denotes keratins
T26037 49521-49523 , denotes ,
T26038 49523-49528 WDT denotes which
T26039 49529-49533 VBD denotes were
T26040 49534-49538 RBR denotes more
T26041 49544-49548 JJ denotes like
T26042 49539-49543 NN denotes skin
T26043 49543-49544 HYPH denotes -
T26044 49549-49553 IN denotes than
T26045 49554-49557 NN denotes TEC
T26046 49558-49562 JJ denotes like
T26047 49557-49558 HYPH denotes -
T26048 49562-49563 . denotes .
T26049 49563-49760 sentence denotes The importance of Apc function in thymic development has been demonstrated by thymocyte-specific loss of Apc by crossing a different strain of Apc conditional mice and LckCre transgenic mice [33].
T26050 49564-49567 DT denotes The
T26051 49568-49578 NN denotes importance
T26052 49626-49638 VBN denotes demonstrated
T26053 49579-49581 IN denotes of
T26054 49582-49585 NN denotes Apc
T26055 49586-49594 NN denotes function
T26056 49595-49597 IN denotes in
T26057 49598-49604 JJ denotes thymic
T26058 49605-49616 NN denotes development
T26059 49617-49620 VBZ denotes has
T26060 49621-49625 VBN denotes been
T26061 49639-49641 IN denotes by
T26062 49642-49651 NN denotes thymocyte
T26063 49652-49660 JJ denotes specific
T26064 49651-49652 HYPH denotes -
T26065 49661-49665 NN denotes loss
T26066 49666-49668 IN denotes of
T26067 49669-49672 NN denotes Apc
T26068 49673-49675 IN denotes by
T26069 49676-49684 VBG denotes crossing
T26070 49685-49686 DT denotes a
T26071 49697-49703 NN denotes strain
T26072 49687-49696 JJ denotes different
T26073 49704-49706 IN denotes of
T26074 49707-49710 NN denotes Apc
T26075 49723-49727 NNS denotes mice
T26076 49711-49722 JJ denotes conditional
T26077 49728-49731 CC denotes and
T26078 49732-49738 NN denotes LckCre
T26079 49750-49754 NNS denotes mice
T26080 49739-49749 JJ denotes transgenic
T26081 49755-49756 -LRB- denotes [
T26082 49756-49758 CD denotes 33
T26083 49758-49759 -RRB- denotes ]
T26084 49759-49760 . denotes .
T26085 49760-49905 sentence denotes Here, by K14-driven TEC-specific loss of Apc, we have demonstrated its importance in thymus development not only in thymocytes but also in TECs.
T26086 49761-49765 RB denotes Here
T26087 49815-49827 VBN denotes demonstrated
T26088 49765-49767 , denotes ,
T26089 49767-49769 IN denotes by
T26090 49770-49773 NN denotes K14
T26091 49774-49780 VBN denotes driven
T26092 49773-49774 HYPH denotes -
T26093 49794-49798 NN denotes loss
T26094 49781-49784 NN denotes TEC
T26095 49785-49793 JJ denotes specific
T26096 49784-49785 HYPH denotes -
T26097 49799-49801 IN denotes of
T26098 49802-49805 NN denotes Apc
T26099 49805-49807 , denotes ,
T26100 49807-49809 PRP denotes we
T26101 49810-49814 VBP denotes have
T26102 49828-49831 PRP$ denotes its
T26103 49832-49842 NN denotes importance
T26104 49843-49845 IN denotes in
T26105 49846-49852 NN denotes thymus
T26106 49853-49864 NN denotes development
T26107 49865-49868 RB denotes not
T26108 49874-49876 IN denotes in
T26109 49869-49873 RB denotes only
T26110 49877-49887 NNS denotes thymocytes
T26111 49888-49891 CC denotes but
T26112 49892-49896 RB denotes also
T26113 49897-49899 IN denotes in
T26114 49900-49904 NNS denotes TECs
T26115 49904-49905 . denotes .
T26116 49905-50133 sentence denotes It is of interest that dental abnormalities, such as supernumerary and impacted teeth similar to those observed in our mutant mice, are frequently seen in patients with Gardner's syndrome, carriers of APC germline mutation [6].
T26117 49906-49908 PRP denotes It
T26118 49909-49911 VBZ denotes is
T26119 49912-49914 IN denotes of
T26120 49915-49923 NN denotes interest
T26121 49924-49928 IN denotes that
T26122 50053-50057 VBN denotes seen
T26123 49929-49935 JJ denotes dental
T26124 49936-49949 NNS denotes abnormalities
T26125 49949-49951 , denotes ,
T26126 49951-49955 JJ denotes such
T26127 49956-49958 IN denotes as
T26128 49959-49972 JJ denotes supernumerary
T26129 49986-49991 NNS denotes teeth
T26130 49973-49976 CC denotes and
T26131 49977-49985 JJ denotes impacted
T26132 49992-49999 JJ denotes similar
T26133 50000-50002 IN denotes to
T26134 50003-50008 DT denotes those
T26135 50009-50017 VBN denotes observed
T26136 50018-50020 IN denotes in
T26137 50021-50024 PRP$ denotes our
T26138 50032-50036 NNS denotes mice
T26139 50025-50031 JJ denotes mutant
T26140 50036-50038 , denotes ,
T26141 50038-50041 VBP denotes are
T26142 50042-50052 RB denotes frequently
T26143 50058-50060 IN denotes in
T26144 50061-50069 NNS denotes patients
T26145 50070-50074 IN denotes with
T26146 50075-50082 NNP denotes Gardner
T26147 50085-50093 NN denotes syndrome
T26148 50082-50084 POS denotes 's
T26149 50093-50095 , denotes ,
T26150 50095-50103 NNS denotes carriers
T26151 50104-50106 IN denotes of
T26152 50107-50110 NN denotes APC
T26153 50120-50128 NN denotes mutation
T26154 50111-50119 NN denotes germline
T26155 50129-50130 -LRB- denotes [
T26156 50130-50131 CD denotes 6
T26157 50131-50132 -RRB- denotes ]
T26158 50132-50133 . denotes .
T26159 50133-50306 sentence denotes The importance of odonto-stomatological examinations should hence be pointed out as a means of reaching a presumptive diagnosis, whose confirmation is vital to the patient.
T26160 50134-50137 DT denotes The
T26161 50138-50148 NN denotes importance
T26162 50203-50210 VBN denotes pointed
T26163 50149-50151 IN denotes of
T26164 50152-50158 NN denotes odonto
T26165 50159-50173 JJ denotes stomatological
T26166 50158-50159 HYPH denotes -
T26167 50174-50186 NNS denotes examinations
T26168 50187-50193 MD denotes should
T26169 50194-50199 RB denotes hence
T26170 50200-50202 VB denotes be
T26171 50211-50214 RP denotes out
T26172 50215-50217 IN denotes as
T26173 50218-50219 DT denotes a
T26174 50220-50225 NN denotes means
T26175 50226-50228 IN denotes of
T26176 50229-50237 VBG denotes reaching
T26177 50238-50239 DT denotes a
T26178 50252-50261 NN denotes diagnosis
T26179 50240-50251 JJ denotes presumptive
T26180 50261-50263 , denotes ,
T26181 50263-50268 WP$ denotes whose
T26182 50269-50281 NN denotes confirmation
T26183 50282-50284 VBZ denotes is
T26184 50285-50290 JJ denotes vital
T26185 50291-50293 IN denotes to
T26186 50294-50297 DT denotes the
T26187 50298-50305 NN denotes patient
T26188 50305-50306 . denotes .
T26189 50306-50555 sentence denotes Further characterization of the mechanism of such developmental defects using our mouse model should provide important insights into Apc function in multiple organ systems and to give better insights into potential adverse events in human subjects.
T26190 50307-50314 JJ denotes Further
T26191 50315-50331 NN denotes characterization
T26192 50408-50415 VB denotes provide
T26193 50332-50334 IN denotes of
T26194 50335-50338 DT denotes the
T26195 50339-50348 NN denotes mechanism
T26196 50349-50351 IN denotes of
T26197 50352-50356 JJ denotes such
T26198 50371-50378 NNS denotes defects
T26199 50357-50370 JJ denotes developmental
T26200 50379-50384 VBG denotes using
T26201 50385-50388 PRP$ denotes our
T26202 50395-50400 NN denotes model
T26203 50389-50394 NN denotes mouse
T26204 50401-50407 MD denotes should
T26205 50416-50425 JJ denotes important
T26206 50426-50434 NNS denotes insights
T26207 50435-50439 IN denotes into
T26208 50440-50443 NN denotes Apc
T26209 50444-50452 NN denotes function
T26210 50453-50455 IN denotes in
T26211 50456-50464 JJ denotes multiple
T26212 50471-50478 NNS denotes systems
T26213 50465-50470 NN denotes organ
T26214 50479-50482 CC denotes and
T26215 50483-50485 TO denotes to
T26216 50486-50490 VB denotes give
T26217 50491-50497 JJR denotes better
T26218 50498-50506 NNS denotes insights
T26219 50507-50511 IN denotes into
T26220 50512-50521 JJ denotes potential
T26221 50530-50536 NNS denotes events
T26222 50522-50529 JJ denotes adverse
T26223 50537-50539 IN denotes in
T26224 50540-50545 JJ denotes human
T26225 50546-50554 NNS denotes subjects
T26226 50554-50555 . denotes .
T26227 50555-50763 sentence denotes In conclusion, we have shown that loss of Apc in K14-expressing embryonic cells causes aberrant morphogenesis in various skin appendages, including hair follicles and teeth, and abnormal thymus organogensis.
T26228 50556-50558 IN denotes In
T26229 50579-50584 VBN denotes shown
T26230 50559-50569 NN denotes conclusion
T26231 50569-50571 , denotes ,
T26232 50571-50573 PRP denotes we
T26233 50574-50578 VBP denotes have
T26234 50585-50589 IN denotes that
T26235 50636-50642 VBZ denotes causes
T26236 50590-50594 NN denotes loss
T26237 50595-50597 IN denotes of
T26238 50598-50601 NN denotes Apc
T26239 50602-50604 IN denotes in
T26240 50605-50608 NN denotes K14
T26241 50609-50619 VBG denotes expressing
T26242 50608-50609 HYPH denotes -
T26243 50630-50635 NNS denotes cells
T26244 50620-50629 JJ denotes embryonic
T26245 50643-50651 JJ denotes aberrant
T26246 50652-50665 NN denotes morphogenesis
T26247 50666-50668 IN denotes in
T26248 50669-50676 JJ denotes various
T26249 50682-50692 NNS denotes appendages
T26250 50677-50681 NN denotes skin
T26251 50692-50694 , denotes ,
T26252 50694-50703 VBG denotes including
T26253 50704-50708 NN denotes hair
T26254 50709-50718 NNS denotes follicles
T26255 50719-50722 CC denotes and
T26256 50723-50728 NNS denotes teeth
T26257 50728-50730 , denotes ,
T26258 50730-50733 CC denotes and
T26259 50734-50742 JJ denotes abnormal
T26260 50750-50762 NN denotes organogensis
T26261 50743-50749 NN denotes thymus
T26262 50762-50763 . denotes .
T26263 50763-50938 sentence denotes Our results provide genetic evidence that expression of Apc is essential for regulation of proper cell fates in these organs that require epithelial–mesenchymal interactions.
T26264 50764-50767 PRP$ denotes Our
T26265 50768-50775 NNS denotes results
T26266 50776-50783 VBP denotes provide
T26267 50784-50791 JJ denotes genetic
T26268 50792-50800 NN denotes evidence
T26269 50801-50805 IN denotes that
T26270 50824-50826 VBZ denotes is
T26271 50806-50816 NN denotes expression
T26272 50817-50819 IN denotes of
T26273 50820-50823 NN denotes Apc
T26274 50827-50836 JJ denotes essential
T26275 50837-50840 IN denotes for
T26276 50841-50851 NN denotes regulation
T26277 50852-50854 IN denotes of
T26278 50855-50861 JJ denotes proper
T26279 50867-50872 NNS denotes fates
T26280 50862-50866 NN denotes cell
T26281 50873-50875 IN denotes in
T26282 50876-50881 DT denotes these
T26283 50882-50888 NNS denotes organs
T26284 50889-50893 WDT denotes that
T26285 50894-50901 VBP denotes require
T26286 50902-50912 JJ denotes epithelial
T26287 50913-50924 JJ denotes mesenchymal
T26288 50912-50913 HYPH denotes
T26289 50925-50937 NNS denotes interactions
T26290 50937-50938 . denotes .
T26537 50963-50975 NN denotes Construction
T26538 50976-50978 IN denotes of
T26539 50979-50988 NN denotes targeting
T26540 50989-50996 NNS denotes vectors
T26541 50996-50997 . denotes .
T26542 50997-51128 sentence denotes To target the Apc locus, we obtained BAC clone RP23-233F17 that contains all the sequence of Apc except for the 5′ UTR and exon 1.
T26543 50998-51000 TO denotes To
T26544 51001-51007 VB denotes target
T26545 51026-51034 VBD denotes obtained
T26546 51008-51011 DT denotes the
T26547 51016-51021 NN denotes locus
T26548 51012-51015 NN denotes Apc
T26549 51021-51023 , denotes ,
T26550 51023-51025 PRP denotes we
T26551 51035-51038 NN denotes BAC
T26552 51039-51044 NN denotes clone
T26553 51045-51049 NN denotes RP23
T26554 51050-51056 NN denotes 233F17
T26555 51049-51050 HYPH denotes -
T26556 51057-51061 WDT denotes that
T26557 51062-51070 VBZ denotes contains
T26558 51071-51074 PDT denotes all
T26559 51079-51087 NN denotes sequence
T26560 51075-51078 DT denotes the
T26561 51088-51090 IN denotes of
T26562 51091-51094 NN denotes Apc
T26563 51095-51101 IN denotes except
T26564 51102-51105 IN denotes for
T26565 51106-51109 DT denotes the
T26566 51113-51116 NN denotes UTR
T26567 51110-51111 CD denotes 5
T26568 51111-51112 SYM denotes
T26569 51117-51120 CC denotes and
T26570 51121-51125 NN denotes exon
T26571 51126-51127 CD denotes 1
T26572 51127-51128 . denotes .
T26573 51128-51270 sentence denotes Using a recombineering-based method for generating conditional mutations [12,13], subcloning of BAC and further modifications were conducted.
T26574 51129-51134 VBG denotes Using
T26575 51260-51269 VBN denotes conducted
T26576 51135-51136 DT denotes a
T26577 51158-51164 NN denotes method
T26578 51137-51151 NN denotes recombineering
T26579 51152-51157 JJ denotes based
T26580 51151-51152 HYPH denotes -
T26581 51165-51168 IN denotes for
T26582 51169-51179 VBG denotes generating
T26583 51180-51191 JJ denotes conditional
T26584 51192-51201 NNS denotes mutations
T26585 51202-51203 -LRB- denotes [
T26586 51206-51208 CD denotes 13
T26587 51203-51205 CD denotes 12
T26588 51205-51206 , denotes ,
T26589 51208-51209 -RRB- denotes ]
T26590 51209-51211 , denotes ,
T26591 51211-51221 NN denotes subcloning
T26592 51222-51224 IN denotes of
T26593 51225-51228 NN denotes BAC
T26594 51229-51232 CC denotes and
T26595 51233-51240 JJ denotes further
T26596 51241-51254 NNS denotes modifications
T26597 51255-51259 VBD denotes were
T26598 51269-51270 . denotes .
T26599 51270-51509 sentence denotes The genomic sequence encompassing Apc exons 11 to 15 was first subcloned into pBR322 vector, and then a loxP site was introduced into intron 13 followed by loxP-FRT-PGKneor-FRT selection cassette into intron14 of the Apc gene (Figure 1A).
T26600 51271-51274 DT denotes The
T26601 51283-51291 NN denotes sequence
T26602 51275-51282 JJ denotes genomic
T26603 51334-51343 VBN denotes subcloned
T26604 51292-51304 VBG denotes encompassing
T26605 51305-51308 NN denotes Apc
T26606 51315-51317 CD denotes 11
T26607 51309-51314 NNS denotes exons
T26608 51318-51320 IN denotes to
T26609 51321-51323 CD denotes 15
T26610 51324-51327 VBD denotes was
T26611 51328-51333 RB denotes first
T26612 51344-51348 IN denotes into
T26613 51349-51355 NN denotes pBR322
T26614 51356-51362 NN denotes vector
T26615 51362-51364 , denotes ,
T26616 51364-51367 CC denotes and
T26617 51368-51372 RB denotes then
T26618 51415-51423 VBN denotes followed
T26619 51373-51374 DT denotes a
T26620 51380-51384 NN denotes site
T26621 51375-51379 NN denotes loxP
T26622 51385-51388 VBD denotes was
T26623 51389-51399 VBN denotes introduced
T26624 51400-51404 IN denotes into
T26625 51405-51411 NN denotes intron
T26626 51412-51414 CD denotes 13
T26627 51424-51426 IN denotes by
T26628 51427-51431 NN denotes loxP
T26629 51432-51435 NN denotes FRT
T26630 51431-51432 HYPH denotes -
T26631 51458-51466 NN denotes cassette
T26632 51435-51436 HYPH denotes -
T26633 51436-51443 NN denotes PGKneor
T26634 51444-51447 NN denotes FRT
T26635 51443-51444 HYPH denotes -
T26636 51448-51457 NN denotes selection
T26637 51467-51471 IN denotes into
T26638 51472-51480 NN denotes intron14
T26639 51481-51483 IN denotes of
T26640 51484-51487 DT denotes the
T26641 51492-51496 NN denotes gene
T26642 51488-51491 NN denotes Apc
T26643 51497-51498 -LRB- denotes (
T26644 51505-51507 NN denotes 1A
T26645 51498-51504 NN denotes Figure
T26646 51507-51508 -RRB- denotes )
T26647 51508-51509 . denotes .
T27080 51511-51521 NN denotes Generation
T27081 51522-51524 IN denotes of
T27082 51525-51531 NN denotes ApcCKO
T27083 51535-51540 NNS denotes cells
T27084 51532-51534 NN denotes ES
T27085 51541-51544 CC denotes and
T27086 51545-51549 NNS denotes mice
T27087 51549-51550 . denotes .
T27088 51550-51648 sentence denotes The linearized targeting vectors were electroporated into 129/S-derived ES cells, WW6 cells [15].
T27089 51551-51554 DT denotes The
T27090 51576-51583 NNS denotes vectors
T27091 51555-51565 VBN denotes linearized
T27092 51566-51575 NN denotes targeting
T27093 51589-51603 VBN denotes electroporated
T27094 51584-51588 VBD denotes were
T27095 51604-51608 IN denotes into
T27096 51609-51612 CD denotes 129
T27097 51613-51614 NN denotes S
T27098 51612-51613 HYPH denotes /
T27099 51615-51622 JJ denotes derived
T27100 51614-51615 HYPH denotes -
T27101 51626-51631 NNS denotes cells
T27102 51623-51625 NN denotes ES
T27103 51631-51633 , denotes ,
T27104 51633-51636 NN denotes WW6
T27105 51637-51642 NNS denotes cells
T27106 51643-51644 -LRB- denotes [
T27107 51644-51646 CD denotes 15
T27108 51646-51647 -RRB- denotes ]
T27109 51647-51648 . denotes .
T27110 51648-51927 sentence denotes All candidate G418-resistant ES clones were screened by long-range gene-specific PCR using Expand Long Template PCR System (Roche, Indianapolis, Indiana, United States), followed by sequencing to validate the correct insertion of the single loxP site and the selection cassette.
T27111 51649-51652 DT denotes All
T27112 51681-51687 NNS denotes clones
T27113 51653-51662 NN denotes candidate
T27114 51663-51667 NN denotes G418
T27115 51668-51677 JJ denotes resistant
T27116 51667-51668 HYPH denotes -
T27117 51678-51680 NN denotes ES
T27118 51693-51701 VBN denotes screened
T27119 51688-51692 VBD denotes were
T27120 51702-51704 IN denotes by
T27121 51705-51709 JJ denotes long
T27122 51710-51715 NN denotes range
T27123 51709-51710 HYPH denotes -
T27124 51730-51733 NN denotes PCR
T27125 51716-51720 NN denotes gene
T27126 51721-51729 JJ denotes specific
T27127 51720-51721 HYPH denotes -
T27128 51734-51739 VBG denotes using
T27129 51740-51746 NNP denotes Expand
T27130 51765-51771 NNP denotes System
T27131 51747-51751 NNP denotes Long
T27132 51752-51760 NNP denotes Template
T27133 51761-51764 NN denotes PCR
T27134 51772-51773 -LRB- denotes (
T27135 51773-51778 NNP denotes Roche
T27136 51778-51780 , denotes ,
T27137 51780-51792 NNP denotes Indianapolis
T27138 51792-51794 , denotes ,
T27139 51794-51801 NNP denotes Indiana
T27140 51801-51803 , denotes ,
T27141 51803-51809 NNP denotes United
T27142 51810-51816 NNP denotes States
T27143 51816-51817 -RRB- denotes )
T27144 51817-51819 , denotes ,
T27145 51819-51827 VBN denotes followed
T27146 51828-51830 IN denotes by
T27147 51831-51841 VBG denotes sequencing
T27148 51842-51844 TO denotes to
T27149 51845-51853 VB denotes validate
T27150 51854-51857 DT denotes the
T27151 51866-51875 NN denotes insertion
T27152 51858-51865 JJ denotes correct
T27153 51876-51878 IN denotes of
T27154 51879-51882 DT denotes the
T27155 51895-51899 NN denotes site
T27156 51883-51889 JJ denotes single
T27157 51890-51894 NN denotes loxP
T27158 51900-51903 CC denotes and
T27159 51904-51907 DT denotes the
T27160 51918-51926 NN denotes cassette
T27161 51908-51917 NN denotes selection
T27162 51926-51927 . denotes .
T27163 51927-52160 sentence denotes Two ES clones with correct ApcCKON/+ modification were injected into C57BL/6J blastocysts, after which chimeric mice with high levels of ES cell contribution were backcrossed to C57BL/6J females to produce heterozygous F1 offspring.
T27164 51928-51931 CD denotes Two
T27165 51935-51941 NNS denotes clones
T27166 51932-51934 NN denotes ES
T27167 51983-51991 VBN denotes injected
T27168 51942-51946 IN denotes with
T27169 51947-51954 JJ denotes correct
T27170 51965-51977 NN denotes modification
T27171 51955-51962 NN denotes ApcCKON
T27172 51962-51963 HYPH denotes /
T27173 51963-51964 SYM denotes +
T27174 51978-51982 VBD denotes were
T27175 51992-51996 IN denotes into
T27176 51997-52002 NN denotes C57BL
T27177 52003-52005 NN denotes 6J
T27178 52002-52003 HYPH denotes /
T27179 52006-52017 NNS denotes blastocysts
T27180 52017-52019 , denotes ,
T27181 52019-52024 IN denotes after
T27182 52091-52102 VBN denotes backcrossed
T27183 52025-52030 WDT denotes which
T27184 52031-52039 JJ denotes chimeric
T27185 52040-52044 NNS denotes mice
T27186 52045-52049 IN denotes with
T27187 52050-52054 JJ denotes high
T27188 52055-52061 NNS denotes levels
T27189 52062-52064 IN denotes of
T27190 52065-52067 NN denotes ES
T27191 52068-52072 NN denotes cell
T27192 52073-52085 NN denotes contribution
T27193 52086-52090 VBD denotes were
T27194 52103-52105 IN denotes to
T27195 52106-52111 NN denotes C57BL
T27196 52112-52114 NN denotes 6J
T27197 52111-52112 HYPH denotes /
T27198 52115-52122 NNS denotes females
T27199 52123-52125 TO denotes to
T27200 52126-52133 VB denotes produce
T27201 52134-52146 JJ denotes heterozygous
T27202 52150-52159 NN denotes offspring
T27203 52147-52149 NN denotes F1
T27204 52159-52160 . denotes .
T27205 52160-52333 sentence denotes The genomic DNA samples obtained from the tail of F1 offspring were subsequently analyzed by Southern blot analysis to further confirm the correct homologous recombination.
T27206 52161-52164 DT denotes The
T27207 52177-52184 NNS denotes samples
T27208 52165-52172 JJ denotes genomic
T27209 52173-52176 NN denotes DNA
T27210 52242-52250 VBN denotes analyzed
T27211 52185-52193 VBN denotes obtained
T27212 52194-52198 IN denotes from
T27213 52199-52202 DT denotes the
T27214 52203-52207 NN denotes tail
T27215 52208-52210 IN denotes of
T27216 52211-52213 NN denotes F1
T27217 52214-52223 NN denotes offspring
T27218 52224-52228 VBD denotes were
T27219 52229-52241 RB denotes subsequently
T27220 52251-52253 IN denotes by
T27221 52254-52262 NNP denotes Southern
T27222 52263-52267 NN denotes blot
T27223 52268-52276 NN denotes analysis
T27224 52277-52279 TO denotes to
T27225 52288-52295 VB denotes confirm
T27226 52280-52287 RB denotes further
T27227 52296-52299 DT denotes the
T27228 52319-52332 NN denotes recombination
T27229 52300-52307 JJ denotes correct
T27230 52308-52318 JJ denotes homologous
T27231 52332-52333 . denotes .
T27232 52333-52516 sentence denotes By crossing the heterozygous mice to FLPe deleter mice [34], PGKneor cassette was deleted in the germline by FRT-mediated recombination to generate mice with the final ApcCKO allele.
T27233 52334-52336 IN denotes By
T27234 52416-52423 VBN denotes deleted
T27235 52337-52345 VBG denotes crossing
T27236 52346-52349 DT denotes the
T27237 52363-52367 NNS denotes mice
T27238 52350-52362 JJ denotes heterozygous
T27239 52368-52370 IN denotes to
T27240 52371-52375 NN denotes FLPe
T27241 52384-52388 NNS denotes mice
T27242 52376-52383 NN denotes deleter
T27243 52389-52390 -LRB- denotes [
T27244 52390-52392 CD denotes 34
T27245 52392-52393 -RRB- denotes ]
T27246 52393-52395 , denotes ,
T27247 52395-52402 NN denotes PGKneor
T27248 52403-52411 NN denotes cassette
T27249 52412-52415 VBD denotes was
T27250 52424-52426 IN denotes in
T27251 52427-52430 DT denotes the
T27252 52431-52439 NN denotes germline
T27253 52440-52442 IN denotes by
T27254 52443-52446 NN denotes FRT
T27255 52447-52455 JJ denotes mediated
T27256 52446-52447 HYPH denotes -
T27257 52456-52469 NN denotes recombination
T27258 52470-52472 TO denotes to
T27259 52473-52481 VB denotes generate
T27260 52482-52486 NNS denotes mice
T27261 52487-52491 IN denotes with
T27262 52492-52495 DT denotes the
T27263 52509-52515 NN denotes allele
T27264 52496-52501 JJ denotes final
T27265 52502-52508 NN denotes ApcCKO
T27266 52515-52516 . denotes .
T27267 52516-52653 sentence denotes ApcCKO heterozygous mice were crossed together to generate homozygous mice, and the homozygous offspring were interbred for maintenance.
T27268 52517-52523 NN denotes ApcCKO
T27269 52537-52541 NNS denotes mice
T27270 52524-52536 JJ denotes heterozygous
T27271 52547-52554 VBN denotes crossed
T27272 52542-52546 VBD denotes were
T27273 52555-52563 RB denotes together
T27274 52564-52566 TO denotes to
T27275 52567-52575 VB denotes generate
T27276 52576-52586 JJ denotes homozygous
T27277 52587-52591 NNS denotes mice
T27278 52591-52593 , denotes ,
T27279 52593-52596 CC denotes and
T27280 52597-52600 DT denotes the
T27281 52612-52621 NN denotes offspring
T27282 52601-52611 JJ denotes homozygous
T27283 52627-52636 VBN denotes interbred
T27284 52622-52626 VBD denotes were
T27285 52637-52640 IN denotes for
T27286 52641-52652 NN denotes maintenance
T27287 52652-52653 . denotes .
T27431 52655-52665 NN denotes Generation
T27432 52666-52668 IN denotes of
T27433 52669-52676 NN denotes ApcΔ580
T27434 52677-52681 NNS denotes mice
T27435 52681-52682 . denotes .
T27436 52682-52904 sentence denotes ApcCKO heterozygote mice were crossed with Cre deleter mice, EIIA-cre transgenic mice that express Cre in early embryo [35], to knockout the Apc allele in the germline, consequently creating a knockout strain (Figure 1A).
T27437 52683-52689 NN denotes ApcCKO
T27438 52703-52707 NNS denotes mice
T27439 52690-52702 NN denotes heterozygote
T27440 52713-52720 VBN denotes crossed
T27441 52708-52712 VBD denotes were
T27442 52721-52725 IN denotes with
T27443 52726-52729 NN denotes Cre
T27444 52738-52742 NNS denotes mice
T27445 52730-52737 NN denotes deleter
T27446 52742-52744 , denotes ,
T27447 52744-52748 NN denotes EIIA
T27448 52749-52752 NN denotes cre
T27449 52748-52749 HYPH denotes -
T27450 52753-52763 JJ denotes transgenic
T27451 52764-52768 NNS denotes mice
T27452 52769-52773 WDT denotes that
T27453 52774-52781 VBP denotes express
T27454 52782-52785 NN denotes Cre
T27455 52786-52788 IN denotes in
T27456 52789-52794 JJ denotes early
T27457 52795-52801 NN denotes embryo
T27458 52802-52803 -LRB- denotes [
T27459 52803-52805 CD denotes 35
T27460 52805-52806 -RRB- denotes ]
T27461 52806-52808 , denotes ,
T27462 52808-52810 TO denotes to
T27463 52811-52819 VB denotes knockout
T27464 52820-52823 DT denotes the
T27465 52828-52834 NN denotes allele
T27466 52824-52827 NN denotes Apc
T27467 52835-52837 IN denotes in
T27468 52838-52841 DT denotes the
T27469 52842-52850 NN denotes germline
T27470 52850-52852 , denotes ,
T27471 52852-52864 RB denotes consequently
T27472 52865-52873 VBG denotes creating
T27473 52874-52875 DT denotes a
T27474 52885-52891 NN denotes strain
T27475 52876-52884 NN denotes knockout
T27476 52892-52893 -LRB- denotes (
T27477 52900-52902 NN denotes 1A
T27478 52893-52899 NN denotes Figure
T27479 52902-52903 -RRB- denotes )
T27480 52903-52904 . denotes .
T27481 52904-52986 sentence denotes The resultant ApcΔ580/+ mice were maintained by backcrossing to C57BL/6J females.
T27482 52905-52908 DT denotes The
T27483 52929-52933 NNS denotes mice
T27484 52909-52918 JJ denotes resultant
T27485 52919-52926 NN denotes ApcΔ580
T27486 52926-52927 HYPH denotes /
T27487 52927-52928 SYM denotes +
T27488 52939-52949 VBN denotes maintained
T27489 52934-52938 VBD denotes were
T27490 52950-52952 IN denotes by
T27491 52953-52965 VBG denotes backcrossing
T27492 52966-52968 IN denotes to
T27493 52969-52974 NN denotes C57BL
T27494 52975-52977 NN denotes 6J
T27495 52974-52975 HYPH denotes /
T27496 52978-52985 NNS denotes females
T27497 52985-52986 . denotes .
T27690 52988-52998 NN denotes Generation
T27691 52999-53001 IN denotes of
T27692 53002-53005 NN denotes K14
T27693 53006-53009 NN denotes cre
T27694 53005-53006 HYPH denotes -
T27695 53022-53026 NNS denotes mice
T27696 53009-53010 : denotes ;
T27697 53011-53017 NN denotes ApcCKO
T27698 53018-53021 NN denotes CKO
T27699 53017-53018 HYPH denotes /
T27700 53026-53027 . denotes .
T27701 53027-53209 sentence denotes The mice analyzed in this study were generated by crossing ApcCKO heterozygote mice of the F1 generation (C57BL/6J × 129/S background) with K14-cre transgenic mice (FVB background).
T27702 53028-53031 DT denotes The
T27703 53032-53036 NNS denotes mice
T27704 53065-53074 VBN denotes generated
T27705 53037-53045 VBN denotes analyzed
T27706 53046-53048 IN denotes in
T27707 53049-53053 DT denotes this
T27708 53054-53059 NN denotes study
T27709 53060-53064 VBD denotes were
T27710 53075-53077 IN denotes by
T27711 53078-53086 VBG denotes crossing
T27712 53087-53093 NN denotes ApcCKO
T27713 53107-53111 NNS denotes mice
T27714 53094-53106 NN denotes heterozygote
T27715 53112-53114 IN denotes of
T27716 53115-53118 DT denotes the
T27717 53122-53132 NN denotes generation
T27718 53119-53121 NN denotes F1
T27719 53133-53134 -LRB- denotes (
T27720 53151-53161 NN denotes background
T27721 53134-53139 NN denotes C57BL
T27722 53140-53142 NN denotes 6J
T27723 53139-53140 HYPH denotes /
T27724 53143-53144 SYM denotes ×
T27725 53145-53148 CD denotes 129
T27726 53149-53150 NN denotes S
T27727 53148-53149 HYPH denotes /
T27728 53161-53162 -RRB- denotes )
T27729 53163-53167 IN denotes with
T27730 53168-53171 NN denotes K14
T27731 53172-53175 NN denotes cre
T27732 53171-53172 HYPH denotes -
T27733 53176-53186 JJ denotes transgenic
T27734 53187-53191 NNS denotes mice
T27735 53192-53193 -LRB- denotes (
T27736 53197-53207 NN denotes background
T27737 53193-53196 NN denotes FVB
T27738 53207-53208 -RRB- denotes )
T27739 53208-53209 . denotes .
T27740 53209-53383 sentence denotes K14-cre; ApcCKO/+ male mice thus generated were then crossed with ApcCKO/CKO females to generate homozygous and heterozygous ApcCKO offspring either with or without K14-cre.
T27741 53210-53213 NN denotes K14
T27742 53214-53217 NN denotes cre
T27743 53213-53214 HYPH denotes -
T27744 53233-53237 NNS denotes mice
T27745 53217-53218 : denotes ;
T27746 53219-53225 NN denotes ApcCKO
T27747 53225-53226 HYPH denotes /
T27748 53226-53227 SYM denotes +
T27749 53228-53232 JJ denotes male
T27750 53263-53270 VBN denotes crossed
T27751 53238-53242 RB denotes thus
T27752 53243-53252 VBN denotes generated
T27753 53253-53257 VBD denotes were
T27754 53258-53262 RB denotes then
T27755 53271-53275 IN denotes with
T27756 53276-53282 NN denotes ApcCKO
T27757 53283-53286 NN denotes CKO
T27758 53282-53283 HYPH denotes /
T27759 53287-53294 NNS denotes females
T27760 53295-53297 TO denotes to
T27761 53298-53306 VB denotes generate
T27762 53307-53317 JJ denotes homozygous
T27763 53342-53351 NN denotes offspring
T27764 53318-53321 CC denotes and
T27765 53322-53334 JJ denotes heterozygous
T27766 53335-53341 NN denotes ApcCKO
T27767 53352-53358 CC denotes either
T27768 53359-53363 IN denotes with
T27769 53364-53366 CC denotes or
T27770 53367-53374 IN denotes without
T27771 53375-53378 NN denotes K14
T27772 53379-53382 NN denotes cre
T27773 53378-53379 HYPH denotes -
T27774 53382-53383 . denotes .
T27775 53383-53438 sentence denotes The mice were intercrossed thereafter for maintenance.
T27776 53384-53387 DT denotes The
T27777 53388-53392 NNS denotes mice
T27778 53398-53410 VBN denotes intercrossed
T27779 53393-53397 VBD denotes were
T27780 53411-53421 RB denotes thereafter
T27781 53422-53425 IN denotes for
T27782 53426-53437 NN denotes maintenance
T27783 53437-53438 . denotes .
T28262 53440-53450 NN denotes Genotyping
T28263 53451-53453 IN denotes of
T28264 53454-53458 NNS denotes mice
T28265 53458-53459 . denotes .
T28266 53459-53771 sentence denotes Genomic DNA from tips of mouse tails obtained at ~10 d of age was genotyped in a single PCR reaction with the following primers: Apc-Int13F2 (GAGAAACCCTGTCTCGAAAAAA) and Apc-Int13R2 (AGTGCTGTTTCTATGAGTCAAC), resulting in 320-bp and 430-bp products from the wild-type and conditional ApcCKO allele, respectively.
T28267 53460-53467 JJ denotes Genomic
T28268 53468-53471 NN denotes DNA
T28269 53526-53535 VBN denotes genotyped
T28270 53472-53476 IN denotes from
T28271 53477-53481 NNS denotes tips
T28272 53482-53484 IN denotes of
T28273 53485-53490 NN denotes mouse
T28274 53491-53496 NNS denotes tails
T28275 53497-53505 VBN denotes obtained
T28276 53506-53508 IN denotes at
T28277 53509-53510 SYM denotes ~
T28278 53510-53512 CD denotes 10
T28279 53513-53514 NNS denotes d
T28280 53515-53517 IN denotes of
T28281 53518-53521 NN denotes age
T28282 53522-53525 VBD denotes was
T28283 53536-53538 IN denotes in
T28284 53539-53540 DT denotes a
T28285 53552-53560 NN denotes reaction
T28286 53541-53547 JJ denotes single
T28287 53548-53551 NN denotes PCR
T28288 53561-53565 IN denotes with
T28289 53566-53569 DT denotes the
T28290 53580-53587 NNS denotes primers
T28291 53570-53579 VBG denotes following
T28292 53587-53589 : denotes :
T28293 53589-53592 NN denotes Apc
T28294 53593-53600 NN denotes Int13F2
T28295 53592-53593 HYPH denotes -
T28296 53601-53602 -LRB- denotes (
T28297 53602-53624 NN denotes GAGAAACCCTGTCTCGAAAAAA
T28298 53624-53625 -RRB- denotes )
T28299 53626-53629 CC denotes and
T28300 53630-53633 NN denotes Apc
T28301 53634-53641 NN denotes Int13R2
T28302 53633-53634 HYPH denotes -
T28303 53642-53643 -LRB- denotes (
T28304 53643-53665 NN denotes AGTGCTGTTTCTATGAGTCAAC
T28305 53665-53666 -RRB- denotes )
T28306 53666-53668 , denotes ,
T28307 53668-53677 VBG denotes resulting
T28308 53678-53680 IN denotes in
T28309 53681-53684 CD denotes 320
T28310 53685-53687 NN denotes bp
T28311 53684-53685 HYPH denotes -
T28312 53699-53707 NNS denotes products
T28313 53688-53691 CC denotes and
T28314 53692-53695 CD denotes 430
T28315 53696-53698 NN denotes bp
T28316 53695-53696 HYPH denotes -
T28317 53708-53712 IN denotes from
T28318 53713-53716 DT denotes the
T28319 53750-53756 NN denotes allele
T28320 53717-53721 JJ denotes wild
T28321 53722-53726 NN denotes type
T28322 53721-53722 HYPH denotes -
T28323 53727-53730 CC denotes and
T28324 53731-53742 JJ denotes conditional
T28325 53743-53749 NN denotes ApcCKO
T28326 53756-53758 , denotes ,
T28327 53758-53770 RB denotes respectively
T28328 53770-53771 . denotes .
T28329 53771-53942 sentence denotes For the detection of Cre-mediated deleted Apc allele, ApcΔ580, the primer Apc-Int14R4 (TTGGCAGACTGTGTATATAAGC) in combination with Apc-Int13F2 resulted in 500-bp product.
T28330 53772-53775 IN denotes For
T28331 53915-53923 VBD denotes resulted
T28332 53776-53779 DT denotes the
T28333 53780-53789 NN denotes detection
T28334 53790-53792 IN denotes of
T28335 53793-53796 NN denotes Cre
T28336 53797-53805 JJ denotes mediated
T28337 53796-53797 HYPH denotes -
T28338 53818-53824 NN denotes allele
T28339 53806-53813 VBN denotes deleted
T28340 53814-53817 NN denotes Apc
T28341 53824-53826 , denotes ,
T28342 53826-53833 NN denotes ApcΔ580
T28343 53833-53835 , denotes ,
T28344 53835-53838 DT denotes the
T28345 53839-53845 NN denotes primer
T28346 53846-53849 NN denotes Apc
T28347 53850-53857 NN denotes Int14R4
T28348 53849-53850 HYPH denotes -
T28349 53858-53859 -LRB- denotes (
T28350 53859-53881 NN denotes TTGGCAGACTGTGTATATAAGC
T28351 53881-53882 -RRB- denotes )
T28352 53883-53885 IN denotes in
T28353 53886-53897 NN denotes combination
T28354 53898-53902 IN denotes with
T28355 53903-53906 NN denotes Apc
T28356 53907-53914 NN denotes Int13F2
T28357 53906-53907 HYPH denotes -
T28358 53924-53926 IN denotes in
T28359 53927-53930 CD denotes 500
T28360 53931-53933 NN denotes bp
T28361 53930-53931 HYPH denotes -
T28362 53934-53941 NN denotes product
T28363 53941-53942 . denotes .
T28364 53942-54105 sentence denotes Primers Cre-F1 (TCCAATTTACTGACCGTACACC) and Cre-R1 (CCGACGATGAAGCATGTTTAG) were used for detection of cre transgene in the germline, resulting in 300-bp products.
T28365 53943-53950 NNS denotes Primers
T28366 53955-53957 NN denotes F1
T28367 53951-53954 NN denotes Cre
T28368 53954-53955 HYPH denotes -
T28369 54023-54027 VBN denotes used
T28370 53958-53959 -LRB- denotes (
T28371 53959-53981 NN denotes TCCAATTTACTGACCGTACACC
T28372 53981-53982 -RRB- denotes )
T28373 53983-53986 CC denotes and
T28374 53987-53990 NN denotes Cre
T28375 53991-53993 NN denotes R1
T28376 53990-53991 HYPH denotes -
T28377 53994-53995 -LRB- denotes (
T28378 53995-54016 NN denotes CCGACGATGAAGCATGTTTAG
T28379 54016-54017 -RRB- denotes )
T28380 54018-54022 VBD denotes were
T28381 54028-54031 IN denotes for
T28382 54032-54041 NN denotes detection
T28383 54042-54044 IN denotes of
T28384 54045-54048 NN denotes cre
T28385 54049-54058 NN denotes transgene
T28386 54059-54061 IN denotes in
T28387 54062-54065 DT denotes the
T28388 54066-54074 NN denotes germline
T28389 54074-54076 , denotes ,
T28390 54076-54085 VBG denotes resulting
T28391 54086-54088 IN denotes in
T28392 54089-54092 CD denotes 300
T28393 54093-54095 NN denotes bp
T28394 54092-54093 HYPH denotes -
T28395 54096-54104 NNS denotes products
T28396 54104-54105 . denotes .
T28397 54105-54337 sentence denotes Amplification was performed in a 25-μl volume containing 15 mM Tris-HCl (pH 8.3), 50 mM KCl, 2.5 mM MgCl2, 0.2 mM dNTP, 0.2μM of each primer, and 1.25 U of AmpliTaq Gold (Applied Biosystems, Foster City, California, United States).
T28398 54106-54119 NN denotes Amplification
T28399 54124-54133 VBN denotes performed
T28400 54120-54123 VBD denotes was
T28401 54134-54136 IN denotes in
T28402 54137-54138 DT denotes a
T28403 54145-54151 NN denotes volume
T28404 54139-54141 CD denotes 25
T28405 54142-54144 NN denotes μl
T28406 54141-54142 HYPH denotes -
T28407 54152-54162 VBG denotes containing
T28408 54163-54165 CD denotes 15
T28409 54166-54168 NNS denotes mM
T28410 54174-54177 NN denotes HCl
T28411 54169-54173 NN denotes Tris
T28412 54173-54174 HYPH denotes -
T28413 54178-54179 -LRB- denotes (
T28414 54179-54181 NN denotes pH
T28415 54182-54185 CD denotes 8.3
T28416 54185-54186 -RRB- denotes )
T28417 54186-54188 , denotes ,
T28418 54188-54190 CD denotes 50
T28419 54191-54193 NNS denotes mM
T28420 54194-54197 NN denotes KCl
T28421 54197-54199 , denotes ,
T28422 54199-54202 CD denotes 2.5
T28423 54203-54205 NNS denotes mM
T28424 54206-54211 NN denotes MgCl2
T28425 54211-54213 , denotes ,
T28426 54213-54216 CD denotes 0.2
T28427 54217-54219 NNS denotes mM
T28428 54220-54224 NN denotes dNTP
T28429 54224-54226 , denotes ,
T28430 54226-54229 CD denotes 0.2
T28431 54229-54231 NNS denotes μM
T28432 54232-54234 IN denotes of
T28433 54235-54239 DT denotes each
T28434 54240-54246 NN denotes primer
T28435 54246-54248 , denotes ,
T28436 54248-54251 CC denotes and
T28437 54252-54256 CD denotes 1.25
T28438 54257-54258 NNS denotes U
T28439 54259-54261 IN denotes of
T28440 54262-54270 NNP denotes AmpliTaq
T28441 54271-54275 NNP denotes Gold
T28442 54276-54277 -LRB- denotes (
T28443 54285-54295 NNP denotes Biosystems
T28444 54277-54284 NNP denotes Applied
T28445 54295-54297 , denotes ,
T28446 54297-54303 NNP denotes Foster
T28447 54304-54308 NNP denotes City
T28448 54308-54310 , denotes ,
T28449 54310-54320 NNP denotes California
T28450 54320-54322 , denotes ,
T28451 54322-54328 NNP denotes United
T28452 54329-54335 NNP denotes States
T28453 54335-54336 -RRB- denotes )
T28454 54336-54337 . denotes .
T28455 54337-54544 sentence denotes The reactions were heated for 10 min at 94 °C to heat-activate the enzyme followed by 30 PCR cycles at 94 °C for 30 s, 58 °C for 30 s, and 72 °C for 45 s, followed by the final extension for 5 min at 72 °C.
T28456 54338-54341 DT denotes The
T28457 54342-54351 NNS denotes reactions
T28458 54357-54363 VBN denotes heated
T28459 54352-54356 VBD denotes were
T28460 54364-54367 IN denotes for
T28461 54368-54370 CD denotes 10
T28462 54371-54374 NNS denotes min
T28463 54375-54377 IN denotes at
T28464 54378-54380 CD denotes 94
T28465 54381-54383 NNS denotes °C
T28466 54384-54386 TO denotes to
T28467 54392-54400 VB denotes activate
T28468 54387-54391 NN denotes heat
T28469 54391-54392 HYPH denotes -
T28470 54401-54404 DT denotes the
T28471 54405-54411 NN denotes enzyme
T28472 54412-54420 VBN denotes followed
T28473 54421-54423 IN denotes by
T28474 54424-54426 CD denotes 30
T28475 54431-54437 NNS denotes cycles
T28476 54427-54430 NN denotes PCR
T28477 54438-54440 IN denotes at
T28478 54441-54443 CD denotes 94
T28479 54444-54446 NNS denotes °C
T28480 54447-54450 IN denotes for
T28481 54451-54453 CD denotes 30
T28482 54454-54455 NN denotes s
T28483 54455-54457 , denotes ,
T28484 54457-54459 CD denotes 58
T28485 54460-54462 NNS denotes °C
T28486 54463-54466 IN denotes for
T28487 54467-54469 CD denotes 30
T28488 54470-54471 NNS denotes s
T28489 54471-54473 , denotes ,
T28490 54473-54476 CC denotes and
T28491 54477-54479 CD denotes 72
T28492 54480-54482 NNS denotes °C
T28493 54483-54486 IN denotes for
T28494 54487-54489 CD denotes 45
T28495 54490-54491 NNS denotes s
T28496 54491-54493 , denotes ,
T28497 54493-54501 VBN denotes followed
T28498 54502-54504 IN denotes by
T28499 54505-54508 DT denotes the
T28500 54515-54524 NN denotes extension
T28501 54509-54514 JJ denotes final
T28502 54525-54528 IN denotes for
T28503 54529-54530 CD denotes 5
T28504 54531-54534 NN denotes min
T28505 54535-54537 IN denotes at
T28506 54538-54540 CD denotes 72
T28507 54541-54543 NNS denotes °C
T28508 54543-54544 . denotes .
T28760 54546-54550 NN denotes Skin
T28761 54551-54563 NN denotes permeability
T28762 54564-54569 NN denotes assay
T28763 54569-54570 . denotes .
T28764 54570-54799 sentence denotes Unfixed and freshly isolated E18.5 embryos were rinsed in PBS and then submerged in X-gal reaction mix at pH 4.5 (100 mM NaPO4, 1.3 mM MgCl2, 3 mM K3Fe(CN)6, 3 mM K4Fe(CN)6, and 1 mg/ml X-gal) at room temperature overnight [36].
T28765 54571-54578 JJ denotes Unfixed
T28766 54606-54613 NNS denotes embryos
T28767 54579-54582 CC denotes and
T28768 54583-54590 RB denotes freshly
T28769 54591-54599 VBN denotes isolated
T28770 54600-54605 NN denotes E18.5
T28771 54619-54625 VBN denotes rinsed
T28772 54614-54618 VBD denotes were
T28773 54626-54628 IN denotes in
T28774 54629-54632 NNS denotes PBS
T28775 54633-54636 CC denotes and
T28776 54637-54641 RB denotes then
T28777 54642-54651 VBD denotes submerged
T28778 54652-54654 IN denotes in
T28779 54655-54656 NN denotes X
T28780 54657-54660 NN denotes gal
T28781 54656-54657 HYPH denotes -
T28782 54670-54673 NN denotes mix
T28783 54661-54669 NN denotes reaction
T28784 54674-54676 IN denotes at
T28785 54677-54679 NN denotes pH
T28786 54680-54683 CD denotes 4.5
T28787 54684-54685 -LRB- denotes (
T28788 54692-54697 NN denotes NaPO4
T28789 54685-54688 CD denotes 100
T28790 54689-54691 NNS denotes mM
T28791 54697-54699 , denotes ,
T28792 54699-54702 CD denotes 1.3
T28793 54703-54705 NNS denotes mM
T28794 54706-54711 NN denotes MgCl2
T28795 54711-54713 , denotes ,
T28796 54713-54714 CD denotes 3
T28797 54715-54717 NN denotes mM
T28798 54718-54722 NN denotes K3Fe
T28799 54722-54723 -LRB- denotes (
T28800 54723-54725 NN denotes CN
T28801 54725-54726 -RRB- denotes )
T28802 54726-54727 CD denotes 6
T28803 54727-54729 , denotes ,
T28804 54729-54730 CD denotes 3
T28805 54731-54733 NN denotes mM
T28806 54734-54738 NN denotes K4Fe
T28807 54738-54739 -LRB- denotes (
T28808 54739-54741 NN denotes CN
T28809 54741-54742 -RRB- denotes )
T28810 54742-54743 CD denotes 6
T28811 54743-54745 , denotes ,
T28812 54745-54748 CC denotes and
T28813 54749-54750 CD denotes 1
T28814 54751-54753 NN denotes mg
T28815 54759-54762 NN denotes gal
T28816 54753-54754 SYM denotes /
T28817 54754-54756 NN denotes ml
T28818 54757-54758 NN denotes X
T28819 54758-54759 HYPH denotes -
T28820 54762-54763 -RRB- denotes )
T28821 54764-54766 IN denotes at
T28822 54767-54771 NN denotes room
T28823 54772-54783 NN denotes temperature
T28824 54784-54793 RB denotes overnight
T28825 54794-54795 -LRB- denotes [
T28826 54795-54797 CD denotes 36
T28827 54797-54798 -RRB- denotes ]
T28828 54798-54799 . denotes .
T28829 54799-54973 sentence denotes At this pH in the absence of epidermal barrier, the solution penetrates epidermis and an endogenous β-galactosidase–like activity catalyzes production of a blue precipitate.
T28830 54800-54802 IN denotes At
T28831 54861-54871 VBZ denotes penetrates
T28832 54803-54807 DT denotes this
T28833 54808-54810 NN denotes pH
T28834 54811-54813 IN denotes in
T28835 54814-54817 DT denotes the
T28836 54818-54825 NN denotes absence
T28837 54826-54828 IN denotes of
T28838 54829-54838 JJ denotes epidermal
T28839 54839-54846 NN denotes barrier
T28840 54846-54848 , denotes ,
T28841 54848-54851 DT denotes the
T28842 54852-54860 NN denotes solution
T28843 54872-54881 NN denotes epidermis
T28844 54882-54885 CC denotes and
T28845 54886-54888 DT denotes an
T28846 54921-54929 NN denotes activity
T28847 54889-54899 JJ denotes endogenous
T28848 54900-54901 JJ denotes β
T28849 54902-54915 NN denotes galactosidase
T28850 54901-54902 HYPH denotes -
T28851 54916-54920 JJ denotes like
T28852 54915-54916 HYPH denotes
T28853 54930-54939 VBZ denotes catalyzes
T28854 54940-54950 NN denotes production
T28855 54951-54953 IN denotes of
T28856 54954-54955 DT denotes a
T28857 54961-54972 NN denotes precipitate
T28858 54956-54960 JJ denotes blue
T28859 54972-54973 . denotes .
T28860 54973-55129 sentence denotes After staining, embryos were washed twice in PBS, fixed overnight at 4 °C in 4% paraformaldehyde, and were photographed using a 35 mm Nikon digital camera.
T28861 54974-54979 IN denotes After
T28862 55003-55009 VBN denotes washed
T28863 54980-54988 NN denotes staining
T28864 54988-54990 , denotes ,
T28865 54990-54997 NNS denotes embryos
T28866 54998-55002 VBD denotes were
T28867 55010-55015 RB denotes twice
T28868 55016-55018 IN denotes in
T28869 55019-55022 NNP denotes PBS
T28870 55022-55024 , denotes ,
T28871 55024-55029 VBN denotes fixed
T28872 55030-55039 RB denotes overnight
T28873 55040-55042 IN denotes at
T28874 55043-55044 CD denotes 4
T28875 55045-55047 NNS denotes °C
T28876 55048-55050 IN denotes in
T28877 55051-55052 CD denotes 4
T28878 55052-55053 NN denotes %
T28879 55054-55070 NN denotes paraformaldehyde
T28880 55070-55072 , denotes ,
T28881 55072-55075 CC denotes and
T28882 55076-55080 VBD denotes were
T28883 55081-55093 VBN denotes photographed
T28884 55094-55099 VBG denotes using
T28885 55100-55101 DT denotes a
T28886 55122-55128 NN denotes camera
T28887 55102-55104 CD denotes 35
T28888 55105-55107 NN denotes mm
T28889 55108-55113 NNP denotes Nikon
T28890 55114-55121 JJ denotes digital
T28891 55128-55129 . denotes .
T29070 55131-55139 JJ denotes Skeletal
T29071 55140-55152 NNS denotes preparations
T29072 55152-55153 . denotes .
T29073 55153-55322 sentence denotes The skinned and eviscerated bodies of the oldest surviving KA mutants (P16–P17) and their age-matched littermates were placed into 1% potassium hydroxide (KOH) for 5 d.
T29074 55154-55157 DT denotes The
T29075 55182-55188 NNS denotes bodies
T29076 55158-55165 VBN denotes skinned
T29077 55166-55169 CC denotes and
T29078 55170-55181 VBN denotes eviscerated
T29079 55273-55279 VBN denotes placed
T29080 55189-55191 IN denotes of
T29081 55192-55195 DT denotes the
T29082 55216-55223 NNS denotes mutants
T29083 55196-55202 JJS denotes oldest
T29084 55203-55212 VBG denotes surviving
T29085 55213-55215 NN denotes KA
T29086 55224-55225 -LRB- denotes (
T29087 55225-55228 NN denotes P16
T29088 55228-55229 SYM denotes
T29089 55229-55232 NN denotes P17
T29090 55232-55233 -RRB- denotes )
T29091 55234-55237 CC denotes and
T29092 55238-55243 PRP$ denotes their
T29093 55256-55267 NNS denotes littermates
T29094 55244-55247 NN denotes age
T29095 55248-55255 JJ denotes matched
T29096 55247-55248 HYPH denotes -
T29097 55268-55272 VBD denotes were
T29098 55280-55284 IN denotes into
T29099 55285-55286 CD denotes 1
T29100 55286-55287 NN denotes %
T29101 55298-55307 NN denotes hydroxide
T29102 55288-55297 NN denotes potassium
T29103 55308-55309 -LRB- denotes (
T29104 55309-55312 NN denotes KOH
T29105 55312-55313 -RRB- denotes )
T29106 55314-55317 IN denotes for
T29107 55318-55319 CD denotes 5
T29108 55320-55321 NNS denotes d
T29109 55321-55322 . denotes .
T29110 55322-55498 sentence denotes The bodies were transferred into a fresh solution of 1% KOH containing a few drops of 0.5% alizarin red S (Sigma, St. Louis, Missouri, United States) and left for another 5 d.
T29111 55323-55326 DT denotes The
T29112 55327-55333 NNS denotes bodies
T29113 55339-55350 VBN denotes transferred
T29114 55334-55338 VBD denotes were
T29115 55351-55355 IN denotes into
T29116 55356-55357 DT denotes a
T29117 55364-55372 NN denotes solution
T29118 55358-55363 JJ denotes fresh
T29119 55373-55375 IN denotes of
T29120 55376-55377 CD denotes 1
T29121 55377-55378 NN denotes %
T29122 55379-55382 NN denotes KOH
T29123 55383-55393 VBG denotes containing
T29124 55394-55395 DT denotes a
T29125 55400-55405 NNS denotes drops
T29126 55396-55399 NN denotes few
T29127 55406-55408 IN denotes of
T29128 55409-55412 CD denotes 0.5
T29129 55412-55413 NN denotes %
T29130 55427-55428 NN denotes S
T29131 55414-55422 NN denotes alizarin
T29132 55423-55426 NN denotes red
T29133 55429-55430 -LRB- denotes (
T29134 55430-55435 NNP denotes Sigma
T29135 55435-55437 , denotes ,
T29136 55437-55440 NNP denotes St.
T29137 55441-55446 NNP denotes Louis
T29138 55446-55448 , denotes ,
T29139 55448-55456 NNP denotes Missouri
T29140 55456-55458 , denotes ,
T29141 55458-55464 NNP denotes United
T29142 55465-55471 NNP denotes States
T29143 55471-55472 -RRB- denotes )
T29144 55473-55476 CC denotes and
T29145 55477-55481 VBN denotes left
T29146 55482-55485 IN denotes for
T29147 55486-55493 DT denotes another
T29148 55496-55497 NN denotes d
T29149 55494-55495 CD denotes 5
T29150 55497-55498 . denotes .
T29151 55498-55583 sentence denotes The stained bodies were stored in glycerin and viewed under a dissection microscope.
T29152 55499-55502 DT denotes The
T29153 55511-55517 NNS denotes bodies
T29154 55503-55510 VBN denotes stained
T29155 55523-55529 VBN denotes stored
T29156 55518-55522 VBD denotes were
T29157 55530-55532 IN denotes in
T29158 55533-55541 NN denotes glycerin
T29159 55542-55545 CC denotes and
T29160 55546-55552 VBN denotes viewed
T29161 55553-55558 IN denotes under
T29162 55559-55560 DT denotes a
T29163 55572-55582 NN denotes microscope
T29164 55561-55571 NN denotes dissection
T29165 55582-55583 . denotes .
T29500 55585-55593 NN denotes Analysis
T29501 55594-55597 IN denotes for
T29502 55598-55604 NN denotes tissue
T29503 55605-55613 JJ denotes specific
T29504 55604-55605 HYPH denotes -
T29505 55614-55627 NN denotes recombination
T29506 55627-55628 . denotes .
T29507 55628-55730 sentence denotes Genotype/tissue-specific recombination of the conditional allele was examined by both PCR and RT-PCR.
T29508 55629-55637 NN denotes Genotype
T29509 55638-55644 NN denotes tissue
T29510 55637-55638 HYPH denotes /
T29511 55645-55653 JJ denotes specific
T29512 55644-55645 HYPH denotes -
T29513 55654-55667 NN denotes recombination
T29514 55698-55706 VBN denotes examined
T29515 55668-55670 IN denotes of
T29516 55671-55674 DT denotes the
T29517 55687-55693 NN denotes allele
T29518 55675-55686 JJ denotes conditional
T29519 55694-55697 VBD denotes was
T29520 55707-55709 IN denotes by
T29521 55710-55714 CC denotes both
T29522 55715-55718 NN denotes PCR
T29523 55719-55722 CC denotes and
T29524 55723-55725 NN denotes RT
T29525 55726-55729 NN denotes PCR
T29526 55725-55726 HYPH denotes -
T29527 55729-55730 . denotes .
T29528 55730-55852 sentence denotes DNA samples extracted from various tissues collected at the time of autopsy were examined by genotyping PCR as described.
T29529 55731-55734 NN denotes DNA
T29530 55735-55742 NNS denotes samples
T29531 55812-55820 VBN denotes examined
T29532 55743-55752 VBN denotes extracted
T29533 55753-55757 IN denotes from
T29534 55758-55765 JJ denotes various
T29535 55766-55773 NNS denotes tissues
T29536 55774-55783 VBN denotes collected
T29537 55784-55786 IN denotes at
T29538 55787-55790 DT denotes the
T29539 55791-55795 NN denotes time
T29540 55796-55798 IN denotes of
T29541 55799-55806 NN denotes autopsy
T29542 55807-55811 VBD denotes were
T29543 55821-55823 IN denotes by
T29544 55824-55834 VBG denotes genotyping
T29545 55835-55838 NN denotes PCR
T29546 55839-55841 IN denotes as
T29547 55842-55851 VBN denotes described
T29548 55851-55852 . denotes .
T29549 55852-56119 sentence denotes RNA extracted from various tissue homogenates in Trizol reagent were examined for expression of wild-type and truncated Apc alleles by SuperScript One-Step RT-PCR with Platinum Taq (Invitrogen, Carlsbad, California, United States), following manufacturer's protocol.
T29550 55853-55856 NN denotes RNA
T29551 55922-55930 VBN denotes examined
T29552 55857-55866 VBN denotes extracted
T29553 55867-55871 IN denotes from
T29554 55872-55879 JJ denotes various
T29555 55887-55898 NNS denotes homogenates
T29556 55880-55886 NN denotes tissue
T29557 55899-55901 IN denotes in
T29558 55902-55908 NN denotes Trizol
T29559 55909-55916 NN denotes reagent
T29560 55917-55921 VBD denotes were
T29561 55931-55934 IN denotes for
T29562 55935-55945 NN denotes expression
T29563 55946-55948 IN denotes of
T29564 55949-55953 JJ denotes wild
T29565 55954-55958 NN denotes type
T29566 55953-55954 HYPH denotes -
T29567 55977-55984 NNS denotes alleles
T29568 55959-55962 CC denotes and
T29569 55963-55972 VBN denotes truncated
T29570 55973-55976 NN denotes Apc
T29571 55985-55987 IN denotes by
T29572 55988-55999 NNP denotes SuperScript
T29573 56012-56015 NN denotes PCR
T29574 56000-56003 CD denotes One
T29575 56004-56008 NNP denotes Step
T29576 56003-56004 HYPH denotes -
T29577 56009-56011 NN denotes RT
T29578 56011-56012 HYPH denotes -
T29579 56016-56020 IN denotes with
T29580 56021-56029 NN denotes Platinum
T29581 56030-56033 NN denotes Taq
T29582 56034-56035 -LRB- denotes (
T29583 56035-56045 NNP denotes Invitrogen
T29584 56045-56047 , denotes ,
T29585 56047-56055 NNP denotes Carlsbad
T29586 56055-56057 , denotes ,
T29587 56057-56067 NNP denotes California
T29588 56067-56069 , denotes ,
T29589 56069-56075 NNP denotes United
T29590 56076-56082 NNP denotes States
T29591 56082-56083 -RRB- denotes )
T29592 56083-56085 , denotes ,
T29593 56085-56094 VBG denotes following
T29594 56095-56107 NN denotes manufacturer
T29595 56110-56118 NN denotes protocol
T29596 56107-56109 POS denotes 's
T29597 56118-56119 . denotes .
T29598 56119-56424 sentence denotes Approximately 200 ng of total RNA from either skin, liver, or thymus from each genotype was reverse-transcribed using primers Apc-F546 (TGAGGAATTTGTCTTGGCGAG) and Apc-R721 (GCACTTCCCATGGCAATCATT), resulting in 528-bp and 313-bp products from the wild-type/ApcCKO alleles and ApcΔ580 allele, respectively.
T29599 56120-56133 RB denotes Approximately
T29600 56138-56140 NNS denotes ng
T29601 56134-56137 CD denotes 200
T29602 56220-56231 VBN denotes transcribed
T29603 56141-56143 IN denotes of
T29604 56144-56149 JJ denotes total
T29605 56150-56153 NN denotes RNA
T29606 56154-56158 IN denotes from
T29607 56159-56165 DT denotes either
T29608 56166-56170 NN denotes skin
T29609 56170-56172 , denotes ,
T29610 56172-56177 NN denotes liver
T29611 56177-56179 , denotes ,
T29612 56179-56181 CC denotes or
T29613 56182-56188 NN denotes thymus
T29614 56189-56193 IN denotes from
T29615 56194-56198 DT denotes each
T29616 56199-56207 NN denotes genotype
T29617 56208-56211 VBD denotes was
T29618 56212-56219 RB denotes reverse
T29619 56219-56220 HYPH denotes -
T29620 56232-56237 VBG denotes using
T29621 56238-56245 NNS denotes primers
T29622 56246-56249 NN denotes Apc
T29623 56250-56254 NN denotes F546
T29624 56249-56250 HYPH denotes -
T29625 56255-56256 -LRB- denotes (
T29626 56256-56277 NN denotes TGAGGAATTTGTCTTGGCGAG
T29627 56277-56278 -RRB- denotes )
T29628 56279-56282 CC denotes and
T29629 56283-56286 NN denotes Apc
T29630 56287-56291 NN denotes R721
T29631 56286-56287 HYPH denotes -
T29632 56292-56293 -LRB- denotes (
T29633 56293-56314 NN denotes GCACTTCCCATGGCAATCATT
T29634 56314-56315 -RRB- denotes )
T29635 56315-56317 , denotes ,
T29636 56317-56326 VBG denotes resulting
T29637 56327-56329 IN denotes in
T29638 56330-56333 CD denotes 528
T29639 56334-56336 NNS denotes bp
T29640 56333-56334 HYPH denotes -
T29641 56348-56356 NNS denotes products
T29642 56337-56340 CC denotes and
T29643 56341-56344 CD denotes 313
T29644 56345-56347 NNS denotes bp
T29645 56344-56345 HYPH denotes -
T29646 56357-56361 IN denotes from
T29647 56362-56365 DT denotes the
T29648 56383-56390 NNS denotes alleles
T29649 56366-56370 JJ denotes wild
T29650 56371-56375 NN denotes type
T29651 56370-56371 HYPH denotes -
T29652 56375-56376 HYPH denotes /
T29653 56376-56382 NN denotes ApcCKO
T29654 56391-56394 CC denotes and
T29655 56395-56402 NN denotes ApcΔ580
T29656 56403-56409 NN denotes allele
T29657 56409-56411 , denotes ,
T29658 56411-56423 RB denotes respectively
T29659 56423-56424 . denotes .
T29758 56426-56430 NN denotes BrdU
T29759 56431-56439 NN denotes labeling
T29760 56439-56440 . denotes .
T29761 56440-56573 sentence denotes Mice were injected intraperitoneally with approximately 50 μg/g body weight of BrdU (Sigma) dissolved in PBS 2 h before their death.
T29762 56441-56445 NNS denotes Mice
T29763 56451-56459 VBN denotes injected
T29764 56446-56450 VBD denotes were
T29765 56460-56477 RB denotes intraperitoneally
T29766 56478-56482 IN denotes with
T29767 56483-56496 RB denotes approximately
T29768 56497-56499 CD denotes 50
T29769 56500-56502 NNS denotes μg
T29770 56510-56516 NN denotes weight
T29771 56502-56503 SYM denotes /
T29772 56503-56504 NN denotes g
T29773 56505-56509 NN denotes body
T29774 56517-56519 IN denotes of
T29775 56520-56524 NN denotes BrdU
T29776 56525-56526 -LRB- denotes (
T29777 56526-56531 NN denotes Sigma
T29778 56531-56532 -RRB- denotes )
T29779 56533-56542 VBN denotes dissolved
T29780 56543-56545 IN denotes in
T29781 56546-56549 NN denotes PBS
T29782 56550-56551 CD denotes 2
T29783 56552-56553 NNS denotes h
T29784 56554-56560 IN denotes before
T29785 56561-56566 PRP$ denotes their
T29786 56567-56572 NN denotes death
T29787 56572-56573 . denotes .
T29788 56573-56644 sentence denotes Tissue samples were fixed in Bouin's and processed as described below.
T29789 56574-56580 NN denotes Tissue
T29790 56581-56588 NNS denotes samples
T29791 56594-56599 VBN denotes fixed
T29792 56589-56593 VBD denotes were
T29793 56600-56602 IN denotes in
T29794 56603-56608 NNP denotes Bouin
T29795 56608-56610 POS denotes 's
T29796 56611-56614 CC denotes and
T29797 56615-56624 VBN denotes processed
T29798 56625-56627 IN denotes as
T29799 56628-56637 VBN denotes described
T29800 56638-56643 RB denotes below
T29801 56643-56644 . denotes .
T30449 56646-56658 JJ denotes Histological
T30450 56678-56686 NN denotes analysis
T30451 56659-56662 CC denotes and
T30452 56663-56677 JJ denotes immunochemical
T30453 56686-56687 . denotes .
T30454 56687-56784 sentence denotes Mutant mice and age-matching littermates were humanely killed at various ages by CO2 inhalation.
T30455 56688-56694 JJ denotes Mutant
T30456 56695-56699 NNS denotes mice
T30457 56743-56749 VBN denotes killed
T30458 56700-56703 CC denotes and
T30459 56704-56707 NN denotes age
T30460 56708-56716 JJ denotes matching
T30461 56707-56708 HYPH denotes -
T30462 56717-56728 NNS denotes littermates
T30463 56729-56733 VBD denotes were
T30464 56734-56742 RB denotes humanely
T30465 56750-56752 IN denotes at
T30466 56753-56760 JJ denotes various
T30467 56761-56765 NNS denotes ages
T30468 56766-56768 IN denotes by
T30469 56769-56772 NN denotes CO2
T30470 56773-56783 NN denotes inhalation
T30471 56783-56784 . denotes .
T30472 56784-57071 sentence denotes Mice were skinned and pieces of skin were either snap-frozen in liquid nitrogen or immediately homogenized in Trizol reagent and stored at −80 °C until molecular analysis, or fixed flat on a piece of paper towel in Bouin's solution for histological and immunohistochemical examinations.
T30473 56785-56789 NNS denotes Mice
T30474 56795-56802 VBN denotes skinned
T30475 56790-56794 VBD denotes were
T30476 56803-56806 CC denotes and
T30477 56807-56813 NNS denotes pieces
T30478 56839-56845 VBN denotes frozen
T30479 56814-56816 IN denotes of
T30480 56817-56821 NN denotes skin
T30481 56822-56826 VBD denotes were
T30482 56827-56833 CC denotes either
T30483 56834-56838 NN denotes snap
T30484 56838-56839 HYPH denotes -
T30485 56846-56848 IN denotes in
T30486 56849-56855 JJ denotes liquid
T30487 56856-56864 NN denotes nitrogen
T30488 56865-56867 CC denotes or
T30489 56868-56879 RB denotes immediately
T30490 56880-56891 VBN denotes homogenized
T30491 56892-56894 IN denotes in
T30492 56895-56901 NNP denotes Trizol
T30493 56902-56909 NN denotes reagent
T30494 56910-56913 CC denotes and
T30495 56914-56920 VBN denotes stored
T30496 56921-56923 IN denotes at
T30497 56924-56925 SYM denotes
T30498 56925-56927 CD denotes 80
T30499 56928-56930 NNS denotes °C
T30500 56931-56936 IN denotes until
T30501 56937-56946 JJ denotes molecular
T30502 56947-56955 NN denotes analysis
T30503 56955-56957 , denotes ,
T30504 56957-56959 CC denotes or
T30505 56960-56965 VBN denotes fixed
T30506 56966-56970 JJ denotes flat
T30507 56971-56973 IN denotes on
T30508 56974-56975 DT denotes a
T30509 56976-56981 NN denotes piece
T30510 56982-56984 IN denotes of
T30511 56985-56990 NN denotes paper
T30512 56991-56996 NN denotes towel
T30513 56997-56999 IN denotes in
T30514 57000-57005 NNP denotes Bouin
T30515 57008-57016 NN denotes solution
T30516 57005-57007 POS denotes 's
T30517 57017-57020 IN denotes for
T30518 57021-57033 JJ denotes histological
T30519 57058-57070 NNS denotes examinations
T30520 57034-57037 CC denotes and
T30521 57038-57057 JJ denotes immunohistochemical
T30522 57070-57071 . denotes .
T30523 57071-57250 sentence denotes The mice were then dissected for gross examination, various tissues were similarly collected for future molecular analyses, and then the whole body was fixed in Bouin's solution.
T30524 57072-57075 DT denotes The
T30525 57076-57080 NNS denotes mice
T30526 57091-57100 VBN denotes dissected
T30527 57081-57085 VBD denotes were
T30528 57086-57090 RB denotes then
T30529 57101-57104 IN denotes for
T30530 57105-57110 JJ denotes gross
T30531 57111-57122 NN denotes examination
T30532 57122-57124 , denotes ,
T30533 57124-57131 JJ denotes various
T30534 57132-57139 NNS denotes tissues
T30535 57155-57164 VBN denotes collected
T30536 57140-57144 VBD denotes were
T30537 57145-57154 RB denotes similarly
T30538 57165-57168 IN denotes for
T30539 57169-57175 JJ denotes future
T30540 57186-57194 NNS denotes analyses
T30541 57176-57185 JJ denotes molecular
T30542 57194-57196 , denotes ,
T30543 57196-57199 CC denotes and
T30544 57200-57204 RB denotes then
T30545 57224-57229 VBN denotes fixed
T30546 57205-57208 DT denotes the
T30547 57215-57219 NN denotes body
T30548 57209-57214 JJ denotes whole
T30549 57220-57223 VBD denotes was
T30550 57230-57232 IN denotes in
T30551 57233-57238 NNP denotes Bouin
T30552 57241-57249 NN denotes solution
T30553 57238-57240 POS denotes 's
T30554 57249-57250 . denotes .
T30555 57250-57366 sentence denotes The samples were then submitted to Rodent Histopathological Core for processing and histopathological examinations.
T30556 57251-57254 DT denotes The
T30557 57255-57262 NNS denotes samples
T30558 57273-57282 VBN denotes submitted
T30559 57263-57267 VBD denotes were
T30560 57268-57272 RB denotes then
T30561 57283-57285 IN denotes to
T30562 57286-57292 NNP denotes Rodent
T30563 57311-57315 NNP denotes Core
T30564 57293-57310 NNP denotes Histopathological
T30565 57316-57319 IN denotes for
T30566 57320-57330 NN denotes processing
T30567 57331-57334 CC denotes and
T30568 57335-57352 JJ denotes histopathological
T30569 57353-57365 NNS denotes examinations
T30570 57365-57366 . denotes .
T30571 57366-57494 sentence denotes For immunohistochemistry, 5-μm paraffin-embedded tissue sections were deparafinized in xylene, followed by alcohol rehydration.
T30572 57367-57370 IN denotes For
T30573 57437-57450 VBN denotes deparafinized
T30574 57371-57391 NN denotes immunohistochemistry
T30575 57391-57393 , denotes ,
T30576 57393-57394 CD denotes 5
T30577 57395-57397 NNS denotes μm
T30578 57394-57395 HYPH denotes -
T30579 57423-57431 NNS denotes sections
T30580 57398-57406 NN denotes paraffin
T30581 57407-57415 VBN denotes embedded
T30582 57406-57407 HYPH denotes -
T30583 57416-57422 NN denotes tissue
T30584 57432-57436 VBD denotes were
T30585 57451-57453 IN denotes in
T30586 57454-57460 NN denotes xylene
T30587 57460-57462 , denotes ,
T30588 57462-57470 VBN denotes followed
T30589 57471-57473 IN denotes by
T30590 57474-57481 NN denotes alcohol
T30591 57482-57493 NN denotes rehydration
T30592 57493-57494 . denotes .
T30593 57494-57726 sentence denotes After quenching endogenous peroxidases in 3% H2O2 in methanol, the slides were rinsed in distilled water, and an antigen retrieval step was carried out in a microwave oven for a total of 10 min in preheated citrate buffer (pH 6.0).
T30594 57495-57500 IN denotes After
T30595 57574-57580 VBN denotes rinsed
T30596 57501-57510 VBG denotes quenching
T30597 57511-57521 JJ denotes endogenous
T30598 57522-57533 NNS denotes peroxidases
T30599 57534-57536 IN denotes in
T30600 57537-57538 CD denotes 3
T30601 57538-57539 NN denotes %
T30602 57540-57544 NN denotes H2O2
T30603 57545-57547 IN denotes in
T30604 57548-57556 NN denotes methanol
T30605 57556-57558 , denotes ,
T30606 57558-57561 DT denotes the
T30607 57562-57568 NNS denotes slides
T30608 57569-57573 VBD denotes were
T30609 57581-57583 IN denotes in
T30610 57584-57593 JJ denotes distilled
T30611 57594-57599 NN denotes water
T30612 57599-57601 , denotes ,
T30613 57601-57604 CC denotes and
T30614 57605-57607 DT denotes an
T30615 57626-57630 NN denotes step
T30616 57608-57615 NN denotes antigen
T30617 57616-57625 NN denotes retrieval
T30618 57635-57642 VBN denotes carried
T30619 57631-57634 VBD denotes was
T30620 57643-57646 RP denotes out
T30621 57647-57649 IN denotes in
T30622 57650-57651 DT denotes a
T30623 57652-57661 NN denotes microwave
T30624 57662-57666 VBN denotes oven
T30625 57667-57670 IN denotes for
T30626 57671-57672 DT denotes a
T30627 57673-57678 NN denotes total
T30628 57679-57681 IN denotes of
T30629 57682-57684 CD denotes 10
T30630 57685-57688 NNS denotes min
T30631 57689-57691 IN denotes in
T30632 57692-57701 JJ denotes preheated
T30633 57710-57716 NN denotes buffer
T30634 57702-57709 NN denotes citrate
T30635 57717-57718 -LRB- denotes (
T30636 57718-57720 NN denotes pH
T30637 57721-57724 CD denotes 6.0
T30638 57724-57725 -RRB- denotes )
T30639 57725-57726 . denotes .
T30640 57726-57812 sentence denotes The slides were then incubated with primary antibodies at room temperature overnight.
T30641 57727-57730 DT denotes The
T30642 57731-57737 NNS denotes slides
T30643 57748-57757 VBN denotes incubated
T30644 57738-57742 VBD denotes were
T30645 57743-57747 RB denotes then
T30646 57758-57762 IN denotes with
T30647 57763-57770 JJ denotes primary
T30648 57771-57781 NNS denotes antibodies
T30649 57782-57784 IN denotes at
T30650 57785-57789 NN denotes room
T30651 57790-57801 NN denotes temperature
T30652 57802-57811 RB denotes overnight
T30653 57811-57812 . denotes .
T30654 57812-58125 sentence denotes Antibodies used were β-catenin (BD Transduction Lab, San Diego, California, United States), keratins 1, 5, 6, 14, involucrin, loricrin (Covance, Berkeley, California, United States), keratin 8 (Abcam, Cambridge, United Kingdom), Ki67 (Vector Laboratories, Burlingame, California, United States) and BrdU (Roche).
T30655 57813-57823 NNS denotes Antibodies
T30656 57829-57833 VBD denotes were
T30657 57824-57828 VBN denotes used
T30658 57834-57835 NN denotes β
T30659 57836-57843 NN denotes catenin
T30660 57835-57836 HYPH denotes -
T30661 57844-57845 -LRB- denotes (
T30662 57861-57864 NNP denotes Lab
T30663 57845-57847 NNP denotes BD
T30664 57848-57860 NNP denotes Transduction
T30665 57864-57866 , denotes ,
T30666 57866-57869 NNP denotes San
T30667 57870-57875 NNP denotes Diego
T30668 57875-57877 , denotes ,
T30669 57877-57887 NNP denotes California
T30670 57887-57889 , denotes ,
T30671 57889-57895 NNP denotes United
T30672 57896-57902 NNP denotes States
T30673 57902-57903 -RRB- denotes )
T30674 57903-57905 , denotes ,
T30675 57905-57913 NNS denotes keratins
T30676 57923-57925 CD denotes 14
T30677 57914-57915 CD denotes 1
T30678 57915-57917 , denotes ,
T30679 57917-57918 CD denotes 5
T30680 57918-57920 , denotes ,
T30681 57920-57921 CD denotes 6
T30682 57921-57923 , denotes ,
T30683 57925-57927 , denotes ,
T30684 57927-57937 NN denotes involucrin
T30685 57937-57939 , denotes ,
T30686 57939-57947 NN denotes loricrin
T30687 57948-57949 -LRB- denotes (
T30688 57949-57956 NNP denotes Covance
T30689 57956-57958 , denotes ,
T30690 57958-57966 NNP denotes Berkeley
T30691 57966-57968 , denotes ,
T30692 57968-57978 NNP denotes California
T30693 57978-57980 , denotes ,
T30694 57980-57986 NNP denotes United
T30695 57987-57993 NNP denotes States
T30696 57993-57994 -RRB- denotes )
T30697 57994-57996 , denotes ,
T30698 57996-58003 NN denotes keratin
T30699 58004-58005 CD denotes 8
T30700 58006-58007 -LRB- denotes (
T30701 58007-58012 NNP denotes Abcam
T30702 58012-58014 , denotes ,
T30703 58014-58023 NNP denotes Cambridge
T30704 58023-58025 , denotes ,
T30705 58025-58031 NNP denotes United
T30706 58032-58039 NNP denotes Kingdom
T30707 58039-58040 -RRB- denotes )
T30708 58040-58042 , denotes ,
T30709 58042-58046 NN denotes Ki67
T30710 58047-58048 -LRB- denotes (
T30711 58055-58067 NNP denotes Laboratories
T30712 58048-58054 NNP denotes Vector
T30713 58067-58069 , denotes ,
T30714 58069-58079 NNP denotes Burlingame
T30715 58079-58081 , denotes ,
T30716 58081-58091 NNP denotes California
T30717 58091-58093 , denotes ,
T30718 58093-58099 NNP denotes United
T30719 58100-58106 NNP denotes States
T30720 58106-58107 -RRB- denotes )
T30721 58108-58111 CC denotes and
T30722 58112-58116 NN denotes BrdU
T30723 58117-58118 -LRB- denotes (
T30724 58118-58123 NNP denotes Roche
T30725 58123-58124 -RRB- denotes )
T30726 58124-58125 . denotes .
T30727 58125-58365 sentence denotes Biotinylated secondary antibodies (donkey anti-rabbit and goat anti-mouse IgG, 1:250; Jackson ImmunoResearch, West Grove, Pennsylvania, United States), followed by the Vectastain Elite ABC kit (Vector Laboratories) were used for detection.
T30728 58126-58138 VBN denotes Biotinylated
T30729 58149-58159 NNS denotes antibodies
T30730 58139-58148 JJ denotes secondary
T30731 58346-58350 VBN denotes used
T30732 58160-58161 -LRB- denotes (
T30733 58220-58234 NNP denotes ImmunoResearch
T30734 58161-58167 NN denotes donkey
T30735 58168-58179 JJ denotes anti-rabbit
T30736 58200-58203 NN denotes IgG
T30737 58180-58183 CC denotes and
T30738 58184-58188 NN denotes goat
T30739 58189-58199 JJ denotes anti-mouse
T30740 58203-58205 , denotes ,
T30741 58205-58206 CD denotes 1
T30742 58206-58207 SYM denotes :
T30743 58207-58210 CD denotes 250
T30744 58210-58211 : denotes ;
T30745 58212-58219 NNP denotes Jackson
T30746 58234-58236 , denotes ,
T30747 58236-58240 NNP denotes West
T30748 58241-58246 NNP denotes Grove
T30749 58246-58248 , denotes ,
T30750 58248-58260 NNP denotes Pennsylvania
T30751 58260-58262 , denotes ,
T30752 58262-58268 NNP denotes United
T30753 58269-58275 NNP denotes States
T30754 58275-58276 -RRB- denotes )
T30755 58276-58278 , denotes ,
T30756 58278-58286 VBN denotes followed
T30757 58287-58289 IN denotes by
T30758 58290-58293 DT denotes the
T30759 58315-58318 NN denotes kit
T30760 58294-58304 NNP denotes Vectastain
T30761 58305-58310 NNP denotes Elite
T30762 58311-58314 NNP denotes ABC
T30763 58319-58320 -LRB- denotes (
T30764 58327-58339 NNP denotes Laboratories
T30765 58320-58326 NNP denotes Vector
T30766 58339-58340 -RRB- denotes )
T30767 58341-58345 VBD denotes were
T30768 58351-58354 IN denotes for
T30769 58355-58364 NN denotes detection
T30770 58364-58365 . denotes .
T30771 58365-58443 sentence denotes The slides were stained with DAB and counterstained with Mayer's hematoxylin.
T30772 58366-58369 DT denotes The
T30773 58370-58376 NNS denotes slides
T30774 58382-58389 VBN denotes stained
T30775 58377-58381 VBD denotes were
T30776 58390-58394 IN denotes with
T30777 58395-58398 NN denotes DAB
T30778 58399-58402 CC denotes and
T30779 58403-58417 VBN denotes counterstained
T30780 58418-58422 IN denotes with
T30781 58423-58428 NNP denotes Mayer
T30782 58431-58442 NN denotes hematoxylin
T30783 58428-58430 POS denotes 's
T30784 58442-58443 . denotes .
T30900 58445-58447 FW denotes In
T30901 58448-58452 FW denotes situ
T30902 58453-58466 NN denotes hybridization
T30903 58466-58467 . denotes .
T30904 58467-58599 sentence denotes Section ISH using rat Shh probe [37] and whole-mount ISH using β-catenin probe [38] were performed as previously described [39,40].
T30905 58468-58475 NN denotes Section
T30906 58476-58479 NN denotes ISH
T30907 58557-58566 VBN denotes performed
T30908 58480-58485 VBG denotes using
T30909 58486-58489 NN denotes rat
T30910 58494-58499 NN denotes probe
T30911 58490-58493 NN denotes Shh
T30912 58500-58501 -LRB- denotes [
T30913 58501-58503 CD denotes 37
T30914 58503-58504 -RRB- denotes ]
T30915 58505-58508 CC denotes and
T30916 58509-58514 JJ denotes whole
T30917 58515-58520 NN denotes mount
T30918 58514-58515 HYPH denotes -
T30919 58521-58524 NN denotes ISH
T30920 58525-58530 VBG denotes using
T30921 58531-58532 NN denotes β
T30922 58533-58540 NN denotes catenin
T30923 58532-58533 HYPH denotes -
T30924 58541-58546 NN denotes probe
T30925 58547-58548 -LRB- denotes [
T30926 58548-58550 CD denotes 38
T30927 58550-58551 -RRB- denotes ]
T30928 58552-58556 VBD denotes were
T30929 58567-58569 IN denotes as
T30930 58581-58590 VBN denotes described
T30931 58570-58580 RB denotes previously
T30932 58591-58592 -LRB- denotes [
T30933 58595-58597 CD denotes 40
T30934 58592-58594 CD denotes 39
T30935 58594-58595 , denotes ,
T30936 58597-58598 -RRB- denotes ]
T30937 58598-58599 . denotes .
T30938 58599-58701 sentence denotes Riboprobes labeled with DIG were detected with BM purple AP substrate precipitation solution (Roche).
T30939 58600-58610 NNS denotes Riboprobes
T30940 58633-58641 VBN denotes detected
T30941 58611-58618 VBN denotes labeled
T30942 58619-58623 IN denotes with
T30943 58624-58627 NN denotes DIG
T30944 58628-58632 VBD denotes were
T30945 58642-58646 IN denotes with
T30946 58647-58649 NN denotes BM
T30947 58650-58656 NN denotes purple
T30948 58684-58692 NN denotes solution
T30949 58657-58659 NN denotes AP
T30950 58660-58669 NN denotes substrate
T30951 58670-58683 NN denotes precipitation
T30952 58693-58694 -LRB- denotes (
T30953 58694-58699 NNP denotes Roche
T30954 58699-58700 -RRB- denotes )
T30955 58700-58701 . denotes .
R7 T566 T567 amod Adenomatous,Coli
R8 T567 T570 nsubjpass Coli,Required
R9 T569 T567 compound Polyposis,Coli
R10 T571 T567 punct (,Coli
R11 T572 T567 appos APC,Coli
R12 T573 T570 punct ),Required
R13 T574 T570 auxpass Is,Required
R14 T575 T570 prep for,Required
R15 T576 T577 amod Normal,Development
R16 T577 T575 pobj Development,for
R17 T578 T577 prep of,Development
R18 T579 T578 pobj Skin,of
R19 T580 T579 cc and,Skin
R20 T581 T579 conj Thymus,Skin
R21 T585 T586 det The,gene
R22 T586 T589 nsubj gene,is
R23 T587 T588 compound tumor,suppressor
R24 T588 T586 compound suppressor,gene
R25 T590 T586 appos Apc,gene
R26 T591 T590 punct (,Apc
R27 T592 T593 nmod adenomatous,coli
R28 T593 T590 appos coli,Apc
R29 T594 T593 nmod polyposis,coli
R30 T595 T589 punct ),is
R31 T596 T597 det a,member
R32 T597 T589 attr member,is
R33 T598 T597 prep of,member
R34 T599 T600 det the,pathway
R35 T600 T598 pobj pathway,of
R36 T601 T600 compound Wnt,pathway
R37 T602 T600 compound signaling,pathway
R38 T603 T604 dep that,involved
R39 T604 T600 relcl involved,pathway
R40 T605 T604 auxpass is,involved
R41 T606 T604 prep in,involved
R42 T607 T606 pobj development,in
R43 T608 T607 cc and,development
R44 T609 T607 conj tumorigenesis,development
R45 T610 T589 punct .,is
R46 T612 T613 amod Heterozygous,knockout
R47 T613 T614 compound knockout,mice
R48 T614 T615 nsubj mice,have
R49 T616 T614 prep for,mice
R50 T617 T616 pobj Apc,for
R51 T618 T619 det a,phenotype
R52 T619 T615 dobj phenotype,have
R53 T620 T621 compound tumor,predisposition
R54 T621 T619 compound predisposition,phenotype
R55 T622 T615 cc and,have
R56 T623 T624 nsubj homozygosity,leads
R57 T624 T615 conj leads,have
R58 T625 T624 prep to,leads
R59 T626 T627 amod embryonic,lethality
R60 T627 T625 pobj lethality,to
R61 T628 T624 punct .,leads
R62 T630 T631 aux To,understand
R63 T631 T632 advcl understand,generated
R64 T633 T634 det the,role
R65 T634 T631 dobj role,understand
R66 T635 T634 prep of,role
R67 T636 T635 pobj Apc,of
R68 T637 T634 prep in,role
R69 T638 T637 pobj development,in
R70 T639 T632 nsubj we,generated
R71 T640 T641 det a,allele
R72 T641 T632 dobj allele,generated
R73 T642 T641 amod floxed,allele
R74 T643 T632 punct .,generated
R75 T645 T646 det These,mice
R76 T646 T647 nsubjpass mice,mated
R77 T648 T647 auxpass were,mated
R78 T649 T647 prep with,mated
R79 T650 T651 det a,strain
R80 T651 T649 pobj strain,with
R81 T652 T651 acl carrying,strain
R82 T653 T654 compound Cre,recombinase
R83 T654 T652 dobj recombinase,carrying
R84 T655 T654 prep under,recombinase
R85 T656 T657 det the,control
R86 T657 T655 pobj control,under
R87 T658 T657 prep of,control
R88 T659 T660 det the,promoter
R90 T661 T660 amod human,promoter
R91 T662 T660 nmod Keratin,promoter
R92 T663 T662 nummod 14,Keratin
R93 T664 T662 punct (,Keratin
R94 T665 T662 appos K14,Keratin
R95 T666 T660 punct ),promoter
R96 T667 T660 punct ", ",promoter
R97 T668 T669 dep which,is
R98 T669 T660 relcl is,promoter
R99 T670 T669 acomp active,is
R100 T671 T669 prep in,is
R101 T672 T673 amod basal,cells
R102 T673 T671 pobj cells,in
R103 T674 T673 prep of,cells
R104 T675 T674 pobj epidermis,of
R105 T676 T675 cc and,epidermis
R106 T677 T678 amod other,epithelia
R107 T678 T675 conj epithelia,epidermis
R108 T679 T678 amod stratified,epithelia
R109 T680 T647 punct .,mated
R110 T682 T683 nsubj Mice,were
R111 T684 T682 amod homozygous,Mice
R112 T685 T684 prep for,homozygous
R113 T686 T687 det the,allele
R114 T687 T685 pobj allele,for
R115 T688 T687 amod floxed,allele
R116 T689 T690 dep that,carry
R117 T690 T682 relcl carry,Mice
R118 T691 T690 advmod also,carry
R119 T692 T693 det the,transgene
R120 T693 T690 dobj transgene,carry
R121 T694 T695 compound K14,cre
R122 T695 T693 compound cre,transgene
R123 T696 T695 punct -,cre
R124 T697 T683 acomp viable,were
R125 T698 T683 cc but,were
R126 T699 T683 conj had,were
R127 T700 T701 amod stunted,growth
R128 T701 T699 dobj growth,had
R129 T702 T699 cc and,had
R130 T703 T699 conj died,had
R131 T704 T703 prep before,died
R132 T705 T704 pobj weaning,before
R133 T706 T683 punct .,were
R134 T708 T709 amod Histological,examinations
R135 T709 T712 nsubj examinations,revealed
R136 T710 T708 cc and,Histological
R137 T711 T708 conj immunochemical,Histological
R138 T713 T714 mark that,resulted
R139 T714 T712 ccomp resulted,revealed
R140 T715 T716 compound K14,cre
R141 T716 T718 npadvmod cre,mediated
R142 T717 T716 punct -,cre
R143 T718 T720 amod mediated,loss
R144 T719 T718 punct –,mediated
R145 T720 T714 nsubj loss,resulted
R146 T721 T720 compound Apc,loss
R147 T722 T714 prep in,resulted
R148 T723 T724 amod aberrant,growth
R149 T724 T722 pobj growth,in
R150 T725 T714 prep in,resulted
R151 T726 T727 amod many,epithelia
R152 T727 T725 pobj epithelia,in
R153 T728 T729 advmod ectodermally,derived
R154 T729 T727 amod derived,epithelia
R155 T730 T727 amod squamous,epithelia
R156 T731 T727 punct ", ",epithelia
R157 T732 T727 prep including,epithelia
R158 T733 T734 compound hair,follicles
R159 T734 T732 pobj follicles,including
R160 T735 T734 punct ", ",follicles
R161 T736 T734 conj teeth,follicles
R162 T737 T736 punct ", ",teeth
R163 T738 T736 cc and,teeth
R164 T739 T740 amod oral,epithelia
R165 T740 T736 conj epithelia,teeth
R166 T741 T739 cc and,oral
R167 T742 T739 conj corneal,oral
R168 T743 T712 punct .,revealed
R169 T745 T746 prep In,observed
R170 T747 T745 pobj addition,In
R171 T748 T746 punct ", ",observed
R172 T749 T750 amod squamous,metaplasia
R173 T750 T746 nsubjpass metaplasia,observed
R174 T751 T746 auxpass was,observed
R175 T752 T746 prep in,observed
R176 T753 T754 amod various,tissues
R177 T754 T752 pobj tissues,in
R178 T755 T756 amod epithelial,derived
R179 T756 T754 amod derived,tissues
R180 T757 T756 punct -,derived
R181 T758 T754 punct ", ",tissues
R182 T759 T754 prep including,tissues
R183 T760 T761 det the,thymus
R184 T761 T759 pobj thymus,including
R185 T762 T746 punct .,observed
R186 T764 T765 det The,growth
R187 T765 T767 nsubj growth,suggest
R188 T766 T765 amod aberrant,growth
R189 T768 T765 prep of,growth
R190 T769 T770 compound hair,follicles
R191 T770 T768 pobj follicles,of
R192 T771 T770 cc and,follicles
R193 T772 T773 amod other,appendages
R194 T773 T770 conj appendages,follicles
R195 T774 T775 advmod as,as
R196 T775 T765 cc as,growth
R197 T776 T775 advmod well,as
R198 T777 T778 det the,abnormalities
R199 T778 T765 conj abnormalities,growth
R200 T779 T778 amod thymic,abnormalities
R201 T780 T778 prep in,abnormalities
R202 T781 T782 nmod K14,cre
R203 T782 T784 nmod cre,mice
R204 T783 T782 punct -,cre
R205 T784 T780 pobj mice,in
R206 T785 T782 punct ;,cre
R207 T786 T787 compound ApcCKO,CKO
R208 T787 T782 appos CKO,cre
R209 T788 T787 punct /,CKO
R210 T789 T790 det the,gene
R211 T790 T792 nsubj gene,is
R212 T791 T790 compound Apc,gene
R213 T792 T767 advcl is,suggest
R214 T793 T792 acomp crucial,is
R215 T794 T792 prep in,is
R216 T795 T796 amod embryonic,cells
R217 T796 T794 pobj cells,in
R218 T797 T798 aux to,specify
R219 T798 T792 xcomp specify,is
R220 T799 T800 amod epithelial,cell
R221 T800 T801 compound cell,fates
R222 T801 T798 dobj fates,specify
R223 T802 T798 prep in,specify
R224 T803 T802 pobj organs,in
R225 T804 T805 dep that,require
R226 T805 T803 relcl require,organs
R227 T806 T807 amod epithelial,mesenchymal
R228 T807 T809 amod mesenchymal,interactions
R229 T808 T807 punct –,mesenchymal
R230 T809 T805 dobj interactions,require
R231 T810 T805 prep for,require
R232 T811 T812 poss their,development
R233 T812 T810 pobj development,for
R234 T813 T767 punct .,suggest
R247 T2364 T2365 amod Adenomatous,coli
R248 T2365 T2367 nsubj coli,is
R249 T2366 T2365 compound polyposis,coli
R250 T2368 T2365 punct (,coli
R251 T2369 T2365 appos APC,coli
R252 T2370 T2367 punct ),is
R253 T2371 T2372 det a,member
R254 T2372 T2367 attr member,is
R255 T2373 T2372 prep of,member
R256 T2374 T2375 det the,pathway
R257 T2375 T2373 pobj pathway,of
R258 T2376 T2375 compound Wnt,pathway
R259 T2377 T2375 compound signaling,pathway
R260 T2378 T2367 cc and,is
R261 T2379 T2380 nsubj one,is
R262 T2380 T2367 conj is,is
R263 T2381 T2379 prep of,one
R264 T2382 T2383 poss its,functions
R265 T2383 T2381 pobj functions,of
R266 T2384 T2383 amod known,functions
R267 T2385 T2386 aux to,regulate
R268 T2386 T2380 xcomp regulate,is
R269 T2387 T2388 det the,levels
R270 T2388 T2386 dobj levels,regulate
R271 T2389 T2388 prep of,levels
R272 T2390 T2391 compound β,catenin
R273 T2391 T2389 pobj catenin,of
R274 T2392 T2391 punct -,catenin
R275 T2393 T2380 punct .,is
R276 T2395 T2396 nsubj Alterations,are
R277 T2397 T2395 prep in,Alterations
R278 T2398 T2399 compound β,catenin
R279 T2399 T2401 compound catenin,regulation
R280 T2400 T2399 punct -,catenin
R281 T2401 T2397 pobj regulation,in
R282 T2402 T2403 advmod very,common
R283 T2403 T2396 acomp common,are
R284 T2404 T2396 prep in,are
R285 T2405 T2406 amod human,tumors
R286 T2406 T2404 pobj tumors,in
R287 T2407 T2408 punct [,1
R288 T2408 T2396 parataxis 1,are
R289 T2409 T2408 punct ],1
R290 T2410 T2396 punct .,are
R291 T2412 T2413 nsubjpass Loss,associated
R292 T2414 T2412 prep of,Loss
R293 T2415 T2414 pobj APC,of
R294 T2416 T2413 auxpass is,associated
R295 T2417 T2413 prep with,associated
R296 T2418 T2417 pobj stabilization,with
R297 T2419 T2418 prep of,stabilization
R298 T2420 T2421 det the,catenin
R299 T2421 T2419 pobj catenin,of
R300 T2422 T2421 amod cytosolic,catenin
R301 T2423 T2421 compound β,catenin
R302 T2424 T2421 punct -,catenin
R303 T2425 T2426 dep that,results
R304 T2426 T2421 relcl results,catenin
R305 T2427 T2426 advmod ultimately,results
R306 T2428 T2426 prep in,results
R307 T2429 T2430 poss its,migration
R308 T2430 T2428 pobj migration,in
R309 T2431 T2430 prep to,migration
R310 T2432 T2433 det the,nucleus
R311 T2433 T2431 pobj nucleus,to
R312 T2434 T2430 cc and,migration
R313 T2435 T2430 conj activating,migration
R314 T2436 T2437 det a,cascade
R315 T2437 T2435 dobj cascade,activating
R316 T2438 T2437 prep of,cascade
R317 T2439 T2438 pobj events,of
R318 T2440 T2437 acl leading,cascade
R319 T2441 T2440 prep to,leading
R320 T2442 T2441 pobj tumorigenesis,to
R321 T2443 T2413 punct .,associated
R322 T2445 T2446 nsubj APC,interacts
R323 T2447 T2446 advmod also,interacts
R324 T2448 T2446 prep with,interacts
R325 T2449 T2450 det a,multitude
R326 T2450 T2448 pobj multitude,with
R327 T2451 T2450 prep of,multitude
R328 T2452 T2453 amod other,proteins
R329 T2453 T2451 pobj proteins,of
R330 T2454 T2453 amod cellular,proteins
R331 T2455 T2453 punct ", ",proteins
R332 T2456 T2453 prep including,proteins
R333 T2457 T2456 pobj axin,including
R334 T2458 T2457 punct -,axin
R335 T2459 T2457 nummod 2,axin
R336 T2460 T2457 punct (,axin
R337 T2461 T2457 appos AXIN2,axin
R338 T2462 T2457 punct ),axin
R339 T2463 T2457 punct ", ",axin
R340 T2464 T2457 conj plakoglobin,axin
R341 T2465 T2464 punct (,plakoglobin
R342 T2466 T2464 appos JUP,plakoglobin
R343 T2467 T2464 punct ),plakoglobin
R344 T2468 T2464 punct ", ",plakoglobin
R345 T2469 T2464 conj Asef,plakoglobin
R346 T2470 T2469 punct (,Asef
R347 T2471 T2469 appos ARHGEF4,Asef
R348 T2472 T2469 punct ),Asef
R349 T2473 T2469 punct ", ",Asef
R350 T2474 T2475 compound kinesin,superfamily
R351 T2475 T2476 npadvmod superfamily,associated
R352 T2476 T2478 amod associated,protein
R353 T2477 T2476 punct –,associated
R354 T2478 T2469 conj protein,Asef
R355 T2479 T2478 nummod 3,protein
R356 T2480 T2478 punct (,protein
R357 T2481 T2478 appos KIFAP3,protein
R358 T2482 T2478 punct ),protein
R359 T2483 T2478 punct ", ",protein
R360 T2484 T2478 conj EB1,protein
R361 T2485 T2484 punct (,EB1
R362 T2486 T2484 appos MAPRE1,EB1
R363 T2487 T2484 punct ),EB1
R364 T2488 T2484 punct ", ",EB1
R365 T2489 T2484 conj microtubules,EB1
R366 T2490 T2489 punct ", ",microtubules
R367 T2491 T2489 cc and,microtubules
R368 T2492 T2493 det the,homolog
R369 T2493 T2489 conj homolog,microtubules
R370 T2494 T2493 amod human,homolog
R371 T2495 T2493 prep of,homolog
R372 T2496 T2497 compound Drosophila,discs
R373 T2497 T2495 pobj discs,of
R374 T2498 T2497 amod large,discs
R375 T2499 T2493 punct (,homolog
R376 T2500 T2493 appos DLG1,homolog
R377 T2501 T2446 punct ),interacts
R378 T2502 T2446 punct .,interacts
R379 T2504 T2505 det These,interactions
R380 T2505 T2506 nsubj interactions,suggest
R381 T2507 T2508 mark that,regulate
R382 T2508 T2506 ccomp regulate,suggest
R383 T2509 T2508 nsubj APC,regulate
R384 T2510 T2508 aux can,regulate
R385 T2511 T2508 advmod potentially,regulate
R386 T2512 T2513 amod many,functions
R387 T2513 T2508 dobj functions,regulate
R388 T2514 T2513 amod cellular,functions
R389 T2515 T2513 punct ", ",functions
R390 T2516 T2513 prep including,functions
R391 T2517 T2518 amod intercellular,adhesion
R392 T2518 T2516 pobj adhesion,including
R393 T2519 T2518 punct ", ",adhesion
R394 T2520 T2521 amod cytoskeletal,organization
R395 T2521 T2518 conj organization,adhesion
R396 T2522 T2521 punct ", ",organization
R397 T2523 T2521 conj regulation,organization
R398 T2524 T2523 prep of,regulation
R399 T2525 T2526 compound plakoglobin,levels
R400 T2526 T2524 pobj levels,of
R401 T2527 T2523 punct ", ",regulation
R402 T2528 T2523 conj regulation,regulation
R403 T2529 T2528 prep of,regulation
R404 T2530 T2531 det the,cycle
R405 T2531 T2529 pobj cycle,of
R406 T2532 T2531 compound cell,cycle
R407 T2533 T2531 cc and,cycle
R408 T2534 T2531 conj apoptosis,cycle
R409 T2535 T2528 punct ", ",regulation
R410 T2536 T2528 conj orientation,regulation
R411 T2537 T2536 prep of,orientation
R412 T2538 T2539 amod asymmetric,division
R413 T2539 T2537 pobj division,of
R414 T2540 T2541 compound stem,cell
R415 T2541 T2539 compound cell,division
R416 T2542 T2536 punct ", ",orientation
R417 T2543 T2536 cc and,orientation
R418 T2544 T2536 conj control,orientation
R419 T2545 T2544 prep of,control
R420 T2546 T2547 compound cell,polarization
R421 T2547 T2545 pobj polarization,of
R422 T2548 T2549 punct [,3
R423 T2549 T2506 parataxis 3,suggest
R424 T2550 T2549 nummod 2,3
R425 T2551 T2549 punct ",",3
R426 T2552 T2549 punct ],3
R427 T2553 T2506 punct .,suggest
R428 T2555 T2556 nsubj APC,is
R429 T2557 T2558 det a,gene
R430 T2558 T2556 attr gene,is
R431 T2559 T2560 compound tumor,suppressor
R432 T2560 T2558 compound suppressor,gene
R433 T2561 T2556 punct .,is
R434 T2563 T2564 amod Somatic,mutations
R435 T2605 T2604 auxpass are,characterized
R436 T2564 T2565 nsubjpass mutations,found
R437 T2606 T2604 agent by,characterized
R438 T2607 T2606 pobj hundreds,by
R439 T2566 T2564 prep in,mutations
R440 T2608 T2607 prep of,hundreds
R441 T2609 T2610 amod adenomatous,polyps
R442 T2610 T2608 pobj polyps,of
R443 T2611 T2610 amod colorectal,polyps
R444 T2612 T2610 punct ", ",polyps
R445 T2613 T2610 prep with,polyps
R446 T2567 T2566 pobj APC,in
R447 T2614 T2615 det an,progression
R448 T2615 T2613 pobj progression,with
R449 T2616 T2617 advmod almost,inevitable
R450 T2617 T2615 amod inevitable,progression
R451 T2568 T2565 auxpass are,found
R452 T2618 T2615 prep to,progression
R453 T2619 T2620 amod colorectal,cancer
R454 T2620 T2618 pobj cancer,to
R455 T2569 T2565 advmod frequently,found
R456 T2621 T2615 prep in,progression
R457 T2622 T2623 det the,decades
R458 T2623 T2621 pobj decades,in
R459 T2570 T2565 prep in,found
R460 T2624 T2623 amod third,decades
R461 T2625 T2624 cc and,third
R462 T2626 T2624 conj fourth,third
R463 T2571 T2572 amod many,tumors
R464 T2627 T2623 prep of,decades
R465 T2628 T2627 pobj life,of
R466 T2629 T2630 punct [,5
R467 T2630 T2604 parataxis 5,characterized
R468 T2572 T2570 pobj tumors,in
R469 T2631 T2630 nummod 4,5
R470 T2632 T2630 punct ",",5
R471 T2633 T2630 punct ],5
R472 T2573 T2572 amod sporadic,tumors
R473 T2634 T2604 punct .,characterized
R474 T2574 T2572 prep of,tumors
R475 T2636 T2637 prep In,develop
R476 T2575 T2576 det the,colon
R477 T2638 T2636 pobj addition,In
R478 T2639 T2638 prep to,addition
R479 T2640 T2641 amod colorectal,neoplams
R480 T2641 T2639 pobj neoplams,to
R481 T2576 T2574 pobj colon,of
R482 T2642 T2637 punct ", ",develop
R483 T2643 T2644 det these,individuals
R484 T2644 T2637 nsubj individuals,develop
R485 T2577 T2576 cc and,colon
R486 T2645 T2637 aux can,develop
R487 T2646 T2647 amod extracolonic,symptoms
R488 T2647 T2637 dobj symptoms,develop
R489 T2648 T2647 punct ", ",symptoms
R490 T2578 T2576 conj rectum,colon
R491 T2649 T2650 prep among,are
R492 T2650 T2647 relcl are,symptoms
R493 T2579 T2565 punct .,found
R494 T2651 T2649 pobj which,among
R495 T2652 T2653 amod upper,tract
R496 T2653 T2655 compound tract,polyps
R497 T2654 T2653 amod gastrointestinal,tract
R498 T2655 T2650 nsubj polyps,are
R499 T2656 T2655 punct ", ",polyps
R500 T2657 T2658 amod congenital,hypertrophy
R501 T2581 T2582 amod Autosomal,mutations
R502 T2658 T2655 conj hypertrophy,polyps
R503 T2659 T2658 prep of,hypertrophy
R504 T2660 T2661 det the,epithelium
R505 T2661 T2659 pobj epithelium,of
R506 T2582 T2585 nsubj mutations,cause
R507 T2662 T2663 amod retinal,pigment
R508 T2663 T2661 compound pigment,epithelium
R509 T2664 T2658 punct ", ",hypertrophy
R510 T2583 T2582 amod dominant,mutations
R511 T2665 T2666 amod desmoid,tumors
R512 T2666 T2658 conj tumors,hypertrophy
R513 T2667 T2666 punct ", ",tumors
R514 T2584 T2582 compound germline,mutations
R515 T2668 T2666 conj disorders,tumors
R516 T2669 T2668 prep of,disorders
R517 T2670 T2671 det the,bones
R518 T2586 T2582 prep in,mutations
R519 T2587 T2586 pobj APC,in
R520 T2671 T2669 pobj bones,of
R521 T2672 T2671 amod maxillary,bones
R522 T2588 T2589 amod familial,polypois
R523 T2673 T2672 cc and,maxillary
R524 T2674 T2672 conj skeletal,maxillary
R525 T2675 T2668 punct ", ",disorders
R526 T2589 T2585 dobj polypois,cause
R527 T2676 T2668 cc and,disorders
R528 T2677 T2678 amod dental,abnormalities
R529 T2590 T2589 amod adenomatous,polypois
R530 T2678 T2668 conj abnormalities,disorders
R531 T2679 T2680 punct [,6
R532 T2680 T2650 parataxis 6,are
R533 T2591 T2589 punct (,polypois
R534 T2681 T2680 punct ],6
R535 T2682 T2650 punct ", ",are
R536 T2683 T2650 advcl suggesting,are
R537 T2592 T2589 appos FAP,polypois
R538 T2684 T2685 det the,importance
R539 T2685 T2683 dobj importance,suggesting
R540 T2686 T2685 prep of,importance
R541 T2593 T2589 punct ),polypois
R542 T2687 T2688 compound APC,gene
R543 T2688 T2686 pobj gene,of
R544 T2689 T2688 nmod functions,gene
R545 T2594 T2589 cc and,polypois
R546 T2690 T2685 prep in,importance
R547 T2691 T2692 det these,systems
R548 T2692 T2690 pobj systems,in
R549 T2693 T2692 compound organ,systems
R550 T2694 T2637 punct .,develop
R551 T2696 T2697 mark Although,is
R552 T2595 T2596 poss its,variant
R553 T2697 T2709 advcl is,understood
R554 T2698 T2699 det the,role
R555 T2699 T2697 nsubj role,is
R556 T2596 T2589 conj variant,polypois
R557 T2700 T2699 prep of,role
R558 T2701 T2700 pobj APC,of
R559 T2702 T2699 prep in,role
R560 T2597 T2596 punct ", ",variant
R561 T2703 T2704 det the,initiation
R562 T2704 T2702 pobj initiation,in
R563 T2705 T2704 prep of,initiation
R564 T2706 T2707 amod human,cancer
R565 T2598 T2599 compound Gardner,syndrome
R566 T2707 T2705 pobj cancer,of
R567 T2708 T2707 amod colorectal,cancer
R568 T2599 T2596 appos syndrome,variant
R569 T2710 T2711 advmod well,established
R570 T2600 T2585 punct .,cause
R571 T2602 T2603 compound FAP,patients
R572 T2603 T2604 nsubjpass patients,characterized
R573 T2711 T2697 acomp established,is
R574 T2817 T2818 amod gastrointestinal,tumor
R575 T2712 T2709 punct ", ",understood
R576 T2713 T2714 poss its,role
R577 T2714 T2709 nsubjpass role,understood
R578 T2715 T2714 prep in,role
R579 T2716 T2717 amod other,processes
R580 T2717 T2715 pobj processes,in
R581 T2818 T2821 compound tumor,predisposition
R582 T2718 T2717 nmod tissue,processes
R583 T2719 T2718 cc and,tissue
R584 T2720 T2718 conj developmental,tissue
R585 T2819 T2817 cc and,gastrointestinal
R586 T2721 T2709 auxpass are,understood
R587 T2722 T2709 neg not,understood
R588 T2723 T2709 advmod well,understood
R589 T2820 T2817 conj other,gastrointestinal
R590 T2724 T2709 punct .,understood
R591 T2726 T2727 prep Given,becomes
R592 T2821 T2816 compound predisposition,phenotype
R593 T2728 T2729 det the,importance
R594 T2729 T2726 pobj importance,Given
R595 T2822 T2823 punct [,7
R596 T2730 T2729 prep of,importance
R597 T2731 T2730 pobj regulation,of
R598 T2732 T2731 prep of,regulation
R599 T2733 T2734 compound Wnt,signaling
R600 T2734 T2732 pobj signaling,of
R601 T2735 T2729 prep in,importance
R602 T2823 T2805 parataxis 7,show
R603 T2736 T2737 amod embryonic,formation
R604 T2737 T2735 pobj formation,in
R605 T2738 T2737 compound pattern,formation
R606 T2824 T2825 punct –,10
R607 T2739 T2737 cc and,formation
R608 T2740 T2737 conj morphogenesis,formation
R609 T2741 T2740 prep of,morphogenesis
R610 T2825 T2823 prep 10,7
R611 T2742 T2743 amod many,organs
R612 T2826 T2823 punct ],7
R613 T2827 T2805 punct .,show
R614 T2743 T2741 pobj organs,of
R615 T2744 T2727 punct ", ",becomes
R616 T2829 T2830 compound Mouse,embryos
R617 T2745 T2746 amod mechanistic,understanding
R618 T2746 T2727 nsubj understanding,becomes
R619 T2747 T2746 prep of,understanding
R620 T2748 T2747 pobj APC,of
R621 T2830 T2831 nsubj embryos,die
R622 T2749 T2748 prep in,APC
R623 T2750 T2749 pobj development,in
R624 T2751 T2749 cc and,in
R625 T2832 T2833 dep that,are
R626 T2752 T2749 conj in,in
R627 T2753 T2754 amod extracolonic,tissues
R628 T2754 T2752 pobj tissues,in
R629 T2755 T2727 acomp critical,becomes
R630 T2756 T2757 aux to,assess
R631 T2833 T2830 relcl are,embryos
R632 T2834 T2833 acomp homozygous,are
R633 T2757 T2755 xcomp assess,critical
R634 T2835 T2834 prep for,homozygous
R635 T2758 T2757 advmod better,assess
R636 T2836 T2837 det the,modification
R637 T2759 T2760 amod potential,events
R638 T2760 T2757 dobj events,assess
R639 T2761 T2760 amod adverse,events
R640 T2762 T2757 prep in,assess
R641 T2837 T2835 pobj modification,for
R642 T2763 T2762 pobj humans,in
R643 T2764 T2727 punct .,becomes
R644 T2838 T2837 amod genetic,modification
R645 T2766 T2767 nummod One,approach
R646 T2767 T2768 nsubj approach,is
R647 T2839 T2831 prep during,die
R648 T2769 T2770 aux to,understand
R649 T2840 T2839 pobj embryogenesis,during
R650 T2770 T2767 advcl understand,approach
R651 T2771 T2772 det the,role
R652 T2772 T2770 dobj role,understand
R653 T2773 T2772 prep of,role
R654 T2774 T2773 pobj Apc,of
R655 T2775 T2772 prep in,role
R656 T2841 T2831 punct ", ",die
R657 T2776 T2775 pobj development,in
R658 T2777 T2778 aux to,develop
R659 T2778 T2768 xcomp develop,is
R660 T2779 T2778 dobj mice,develop
R661 T2842 T2831 cc and,die
R662 T2780 T2779 prep with,mice
R663 T2781 T2782 det an,mutation
R664 T2843 T2844 nsubj some,survive
R665 T2782 T2780 pobj mutation,with
R666 T2783 T2782 amod inactivating,mutation
R667 T2784 T2782 compound Apc,mutation
R668 T2844 T2831 conj survive,die
R669 T2785 T2768 punct .,is
R670 T2787 T2788 amod Several,strains
R671 T2788 T2792 nsubjpass strains,described
R672 T2845 T2843 prep of,some
R673 T2789 T2790 advmod genetically,modified
R674 T2790 T2788 amod modified,strains
R675 T2791 T2788 compound mouse,strains
R676 T2846 T2847 det the,models
R677 T2793 T2788 prep for,strains
R678 T2794 T2793 pobj Apc,for
R679 T2847 T2845 pobj models,of
R680 T2795 T2792 aux have,described
R681 T2796 T2792 auxpass been,described
R682 T2797 T2798 punct [,7
R683 T2848 T2844 aux do,survive
R684 T2798 T2792 parataxis 7,described
R685 T2799 T2800 punct –,10
R686 T2800 T2798 prep 10,7
R687 T2801 T2798 punct ],7
R688 T2849 T2844 neg not,survive
R689 T2802 T2792 punct .,described
R690 T2850 T2844 prep beyond,survive
R691 T2804 T2805 nsubj Most,show
R692 T2806 T2804 prep of,Most
R693 T2851 T2850 pobj gastrulation,beyond
R694 T2807 T2808 det these,models
R695 T2808 T2806 pobj models,of
R696 T2809 T2804 punct ", ",Most
R697 T2810 T2804 prep in,Most
R698 T2852 T2853 punct [,11
R699 T2811 T2812 det the,state
R700 T2812 T2810 pobj state,in
R701 T2813 T2812 amod heterozygous,state
R702 T2853 T2844 parataxis 11,survive
R703 T2814 T2805 punct ", ",show
R704 T2815 T2816 det a,phenotype
R705 T2816 T2805 dobj phenotype,show
R706 T2854 T2853 nummod 8,11
R707 T2855 T2853 punct ",",11
R708 T2856 T2853 punct ],11
R709 T2923 T2911 nsubj we,generated
R710 T2924 T2911 dobj mice,generated
R711 T2925 T2924 acl containing,mice
R712 T2857 T2844 punct .,survive
R713 T2926 T2927 det a,allele
R714 T2859 T2860 det An,approach
R715 T2927 T2925 dobj allele,containing
R716 T2928 T2929 amod conditional,knockout
R717 T2929 T2927 nmod knockout,allele
R718 T2930 T2929 punct (,knockout
R719 T2860 T2862 nsubj approach,is
R720 T2931 T2929 appos CKO,knockout
R721 T2932 T2927 punct ),allele
R722 T2861 T2860 amod alternate,approach
R723 T2933 T2927 amod mutant,allele
R724 T2934 T2927 prep of,allele
R725 T2935 T2934 pobj Apc,of
R726 T2863 T2864 aux to,understand
R727 T2936 T2927 punct (,allele
R728 T2937 T2927 appos ApcCKO,allele
R729 T2938 T2911 punct ),generated
R730 T2939 T2911 punct .,generated
R731 T2864 T2860 advcl understand,approach
R732 T2941 T2942 det These,mice
R733 T2865 T2866 det the,role
R734 T2942 T2943 nsubjpass mice,mated
R735 T2944 T2943 auxpass were,mated
R736 T2866 T2864 dobj role,understand
R737 T2945 T2943 prep with,mated
R738 T2946 T2947 det a,strain
R739 T2947 T2945 pobj strain,with
R740 T2948 T2947 acl carrying,strain
R741 T2867 T2866 prep of,role
R742 T2949 T2950 compound Cre,recombinase
R743 T2950 T2948 dobj recombinase,carrying
R744 T2868 T2867 pobj Apc,of
R745 T2951 T2950 prep under,recombinase
R746 T2869 T2866 prep in,role
R747 T2952 T2953 det the,control
R748 T2953 T2951 pobj control,under
R749 T2954 T2953 prep of,control
R750 T2955 T2956 det the,promoter
R751 T2870 T2869 pobj development,in
R752 T2956 T2954 pobj promoter,of
R753 T2957 T2956 amod human,promoter
R754 T2958 T2956 nmod Keratin,promoter
R755 T2871 T2869 cc and,in
R756 T2959 T2958 nummod 14,Keratin
R757 T2960 T2958 punct (,Keratin
R758 T2961 T2958 appos K14,Keratin
R759 T2962 T2956 punct ),promoter
R760 T2963 T2956 punct ", ",promoter
R761 T2964 T2965 dep which,is
R762 T2872 T2871 punct /,and
R763 T2965 T2956 relcl is,promoter
R764 T2966 T2965 acomp active,is
R765 T2967 T2965 prep in,is
R766 T2873 T2871 cc or,and
R767 T2968 T2969 amod basal,cells
R768 T2969 T2967 pobj cells,in
R769 T2970 T2969 prep of,cells
R770 T2874 T2869 conj in,in
R771 T2971 T2970 pobj epidermis,of
R772 T2972 T2971 cc and,epidermis
R773 T2973 T2974 amod other,epithelia
R774 T2875 T2876 amod specific,tissues
R775 T2974 T2971 conj epithelia,epidermis
R776 T2975 T2974 amod stratified,epithelia
R777 T2976 T2943 punct .,mated
R778 T2876 T2874 pobj tissues,in
R779 T2978 T2979 nsubj We,report
R780 T2877 T2878 aux to,generate
R781 T2980 T2979 advmod here,report
R782 T2981 T2982 mark that,resulted
R783 T2982 T2979 ccomp resulted,report
R784 T2878 T2862 xcomp generate,is
R785 T2983 T2984 compound K14,promoter
R786 T2984 T2985 npadvmod promoter,driven
R787 T2985 T2987 amod driven,loss
R788 T2879 T2880 det a,strain
R789 T2986 T2985 punct -,driven
R790 T2987 T2982 nsubj loss,resulted
R791 T2988 T2987 prep of,loss
R792 T2880 T2878 dobj strain,generate
R793 T2989 T2988 pobj Apc,of
R794 T2990 T2982 prep in,resulted
R795 T2881 T2880 compound mouse,strain
R796 T2991 T2992 amod aberrant,development
R797 T2992 T2990 pobj development,in
R798 T2993 T2992 prep of,development
R799 T2882 T2883 dep that,carries
R800 T2994 T2995 amod several,organs
R801 T2995 T2993 pobj organs,of
R802 T2996 T2997 dep that,require
R803 T2883 T2880 relcl carries,strain
R804 T2997 T2995 relcl require,organs
R805 T2998 T2999 amod inductive,interactions
R806 T2999 T2997 dobj interactions,require
R807 T3000 T3001 amod epithelial,mesenchymal
R808 T3001 T2999 amod mesenchymal,interactions
R809 T3002 T3001 punct –,mesenchymal
R810 T3003 T2995 punct ", ",organs
R811 T2884 T2885 det a,allele
R812 T3004 T2995 prep including,organs
R813 T3005 T3006 compound hair,follicle
R814 T3006 T3004 pobj follicle,including
R815 T2885 T2883 dobj allele,carries
R816 T3007 T3006 punct ", ",follicle
R817 T3008 T3006 conj teeth,follicle
R818 T3009 T3008 punct ", ",teeth
R819 T2886 T2887 advmod conditionally,modified
R820 T3010 T3008 cc and,teeth
R821 T3011 T3008 conj thymus,teeth
R822 T3012 T2982 punct ", ",resulted
R823 T2887 T2885 amod modified,allele
R824 T3013 T2982 cc and,resulted
R825 T3014 T2982 conj resulted,resulted
R826 T2888 T2878 cc and,generate
R827 T2889 T2878 conj mate,generate
R828 T3015 T3014 prep in,resulted
R829 T2890 T2889 dobj it,mate
R830 T3016 T3017 amod neonatal,death
R831 T3017 T3015 pobj death,in
R832 T3018 T3014 prep in,resulted
R833 T2891 T2889 prep with,mate
R834 T3019 T3018 pobj mice,in
R835 T3020 T2979 punct .,report
R836 T2892 T2893 det a,strain
R837 T3022 T3023 nsubj We,found
R838 T3024 T3025 mark that,plays
R839 T2893 T2891 pobj strain,with
R840 T3025 T3023 ccomp plays,found
R841 T3026 T3025 nsubj Apc,plays
R842 T2894 T2893 compound mouse,strain
R843 T3027 T3028 det a,role
R844 T3028 T3025 dobj role,plays
R845 T2895 T2896 dep that,facilitates
R846 T2896 T2893 relcl facilitates,strain
R847 T2897 T2898 det the,modification
R848 T3029 T3028 amod crucial,role
R849 T3030 T3025 prep in,plays
R850 T3031 T3030 pobj determinations,in
R851 T2898 T2896 dobj modification,facilitates
R852 T3032 T3031 prep of,determinations
R853 T3033 T3034 compound cell,fates
R854 T2899 T2898 prep of,modification
R855 T3034 T3032 pobj fates,of
R856 T3035 T3025 prep during,plays
R857 T2900 T2901 det the,allele
R858 T3036 T3037 det the,development
R859 T3037 T3035 pobj development,during
R860 T3038 T3037 amod embryonic,development
R861 T3039 T3025 punct ", ",plays
R862 T3040 T3041 advmod possibly,via
R863 T3041 T3025 prep via,plays
R864 T2901 T2899 pobj allele,of
R865 T3042 T3043 amod temporal,regulation
R866 T3043 T3041 pobj regulation,via
R867 T3044 T3042 cc and,temporal
R868 T3045 T3046 npadvmod tissue,specific
R869 T2902 T2901 amod conditional,allele
R870 T3046 T3042 conj specific,temporal
R871 T3047 T3046 punct -,specific
R872 T3048 T3043 prep of,regulation
R873 T2903 T2898 prep in,modification
R874 T3049 T3050 compound β,catenin
R875 T3050 T3052 compound catenin,levels
R876 T2904 T2905 amod specific,lineages
R877 T3051 T3050 punct -,catenin
R878 T3052 T3048 pobj levels,of
R879 T3053 T3052 prep in,levels
R880 T2905 T2903 pobj lineages,in
R881 T3054 T3055 det the,skin
R882 T3055 T3053 pobj skin,in
R883 T3056 T3055 punct ", ",skin
R884 T2906 T2905 compound cell,lineages
R885 T3057 T3058 poss its,appendages
R886 T3058 T3055 appos appendages,skin
R887 T3059 T3053 punct ", ",in
R888 T2907 T2862 punct .,is
R889 T3060 T3053 cc and,in
R890 T3061 T3053 conj in,in
R891 T3062 T3063 det the,thymus
R892 T2909 T2910 aux To,assess
R893 T3063 T3061 pobj thymus,in
R894 T3064 T3023 punct .,found
R895 T2910 T2911 advcl assess,generated
R896 T2912 T2913 det the,role
R897 T2913 T2910 dobj role,assess
R898 T2914 T2913 prep of,role
R899 T2915 T2914 pobj Apc,of
R900 T2916 T2913 prep in,role
R901 T2917 T2918 amod different,stages
R902 T2918 T2916 pobj stages,in
R903 T2919 T2918 prep of,stages
R904 T2920 T2919 pobj life,of
R905 T2921 T2910 advmod systematically,assess
R906 T2922 T2911 punct ", ",generated
R918 T4598 T4597 prep of,Generation
R919 T4599 T4600 det the,Mice
R920 T4600 T4598 pobj Mice,of
R921 T4601 T4600 nmod ApcCKO,Mice
R922 T4602 T4601 cc and,ApcCKO
R923 T4603 T4601 conj ApcΔ580,ApcCKO
R924 T4605 T4606 aux To,investigate
R925 T4606 T4607 advcl investigate,used
R926 T4608 T4609 det the,role
R927 T4609 T4606 dobj role,investigate
R928 T4610 T4609 prep of,role
R929 T4611 T4610 pobj Apc,of
R930 T4612 T4609 prep in,role
R931 T4613 T4612 pobj development,in
R932 T4614 T4613 prep of,development
R933 T4615 T4614 pobj skin,of
R934 T4616 T4615 cc and,skin
R935 T4617 T4618 poss its,appendages
R936 T4618 T4615 conj appendages,skin
R937 T4619 T4607 punct ", ",used
R938 T4620 T4607 nsubj we,used
R939 T4621 T4622 det the,technology
R940 T4622 T4607 dobj technology,used
R941 T4623 T4624 compound Cre,loxP
R942 T4624 T4622 compound loxP,technology
R943 T4625 T4624 punct /,loxP
R944 T4626 T4627 aux to,introduce
R945 T4627 T4607 advcl introduce,used
R946 T4628 T4629 det a,mutation
R947 T4629 T4627 dobj mutation,introduce
R948 T4630 T4629 amod conditional,mutation
R949 T4631 T4629 prep of,mutation
R950 T4632 T4633 det the,gene
R951 T4633 T4631 pobj gene,of
R952 T4634 T4633 compound Apc,gene
R953 T4635 T4627 prep in,introduce
R954 T4636 T4635 pobj mice,in
R955 T4637 T4607 punct .,used
R956 T4639 T4640 nsubj We,constructed
R957 T4641 T4642 amod embryonic,stem
R958 T4642 T4643 nmod stem,cells
R959 T4643 T4640 dobj cells,constructed
R960 T4644 T4642 punct (,stem
R961 T4645 T4642 appos ES,stem
R962 T4646 T4643 punct ),cells
R963 T4647 T4643 cc and,cells
R964 T4648 T4643 conj mice,cells
R965 T4649 T4648 acl carrying,mice
R966 T4650 T4651 det an,allele
R967 T4651 T4649 dobj allele,carrying
R968 T4652 T4651 compound Apc,allele
R969 T4653 T4651 acl harboring,allele
R970 T4654 T4655 preconj both,pair
R971 T4655 T4653 dobj pair,harboring
R972 T4656 T4655 det a,pair
R973 T4657 T4655 prep of,pair
R974 T4658 T4659 compound loxP,sites
R975 T4659 T4657 pobj sites,of
R976 T4660 T4655 acl flanking,pair
R977 T4661 T4662 compound Apc,exon
R978 T4662 T4660 dobj exon,flanking
R979 T4663 T4662 nummod 14,exon
R980 T4664 T4655 cc and,pair
R981 T4665 T4666 det a,pair
R982 T4666 T4655 conj pair,pair
R983 T4667 T4666 prep of,pair
R984 T4668 T4669 nmod FLP,target
R985 T4669 T4671 nmod target,sites
R986 T4670 T4669 nmod recognition,target
R987 T4671 T4667 pobj sites,of
R988 T4672 T4669 punct (,target
R989 T4673 T4669 appos FRT,target
R990 T4674 T4671 punct ),sites
R991 T4675 T4666 acl flanking,pair
R992 T4676 T4677 compound PGK,neomycin
R993 T4677 T4679 compound neomycin,cassette
R994 T4678 T4677 punct -,neomycin
R995 T4679 T4675 dobj cassette,flanking
R996 T4680 T4679 compound selection,cassette
R997 T4681 T4640 prep by,constructed
R998 T4682 T4681 pobj recombineering,by
R999 T4683 T4684 punct [,13
R1000 T4684 T4640 parataxis 13,constructed
R1001 T4685 T4684 nummod 12,13
R1002 T4686 T4684 punct ",",13
R1003 T4687 T4684 punct ],13
R1004 T4688 T4689 punct (,N
R1005 T4689 T4640 parataxis N,constructed
R1006 T4690 T4691 compound Figure,1A
R1007 T4691 T4689 dep 1A,N
R1008 T4692 T4689 punct ", ",N
R1009 T4693 T4694 compound ApcCKON,allele
R1010 T4694 T4689 dep allele,N
R1011 T4695 T4689 punct ", ",N
R1012 T4696 T4689 prep for,N
R1013 T4697 T4698 compound neomycin,cassette
R1014 T4698 T4696 pobj cassette,for
R1015 T4699 T4689 punct ),N
R1016 T4700 T4640 punct .,constructed
R1017 T4702 T4703 det A,cassette
R1018 T4703 T4707 nsubjpass cassette,inserted
R1019 T4704 T4705 compound PGK,neomycin
R1020 T4705 T4703 compound neomycin,cassette
R1021 T4706 T4705 punct -,neomycin
R1022 T4708 T4707 auxpass was,inserted
R1023 T4709 T4707 prep in,inserted
R1024 T4710 T4711 det the,orientation
R1025 T4711 T4709 pobj orientation,in
R1026 T4712 T4711 amod same,orientation
R1027 T4713 T4711 amod transcriptional,orientation
R1028 T4714 T4711 prep as,orientation
R1029 T4715 T4714 pobj Apc,as
R1030 T4716 T4707 prep in,inserted
R1031 T4717 T4716 pobj intron,in
R1032 T4718 T4717 nummod 14,intron
R1033 T4719 T4717 prep of,intron
R1034 T4720 T4721 det the,gene
R1035 T4721 T4719 pobj gene,of
R1036 T4722 T4721 amod endogenous,gene
R1037 T4723 T4707 punct .,inserted
R1038 T4725 T4726 det The,sites
R1039 T4726 T4730 nsubjpass sites,used
R1040 T4727 T4726 nmod loxP,sites
R1041 T4728 T4727 cc and,loxP
R1042 T4729 T4727 conj FRT,loxP
R1043 T4731 T4730 auxpass were,used
R1044 T4732 T4733 aux to,aid
R1045 T4733 T4730 advcl aid,used
R1046 T4734 T4735 amod unidirectional,recombination
R1047 T4735 T4733 dobj recombination,aid
R1048 T4736 T4737 punct [,13
R1049 T4737 T4730 parataxis 13,used
R1050 T4738 T4737 nummod 12,13
R1051 T4739 T4737 punct ",",13
R1052 T4740 T4737 punct ],13
R1053 T4741 T4730 punct .,used
R1054 T4743 T4744 nummod Two,lines
R1055 T4744 T4746 nsubjpass lines,generated
R1056 T4745 T4744 compound mouse,lines
R1057 T4747 T4744 acl containing,lines
R1058 T4748 T4749 det the,modification
R1059 T4749 T4747 dobj modification,containing
R1060 T4750 T4749 amod same,modification
R1061 T4751 T4746 auxpass were,generated
R1062 T4752 T4746 prep from,generated
R1063 T4753 T4754 nummod two,clones
R1064 T4754 T4752 pobj clones,from
R1065 T4755 T4754 amod independent,clones
R1066 T4756 T4754 compound ES,clones
R1067 T4757 T4758 aux to,ensure
R1068 T4758 T4746 advcl ensure,generated
R1069 T4759 T4760 mark that,behave
R1070 T4760 T4758 ccomp behave,ensure
R1071 T4761 T4762 det these,lines
R1072 T4762 T4760 nsubj lines,behave
R1073 T4763 T4762 nummod two,lines
R1074 T4764 T4760 prep in,behave
R1075 T4765 T4766 det the,way
R1076 T4766 T4764 pobj way,in
R1077 T4767 T4766 amod same,way
R1078 T4768 T4746 punct .,generated
R1079 T4770 T4771 det These,mice
R1080 T4771 T4775 nsubjpass mice,crossed
R1081 T4772 T4771 nmod ApcCKON,mice
R1082 T4773 T4772 punct /,ApcCKON
R1083 T4774 T4772 punct +,ApcCKON
R1084 T4776 T4775 auxpass were,crossed
R1085 T4777 T4775 prep with,crossed
R1086 T4778 T4779 compound FLPe,deleter
R1087 T4779 T4777 pobj deleter,with
R1088 T4780 T4779 punct -,deleter
R1089 T4781 T4782 aux to,generate
R1090 T4782 T4775 advcl generate,crossed
R1091 T4783 T4784 nmod ApcCKO,mice
R1092 T4784 T4782 dobj mice,generate
R1093 T4785 T4783 punct /,ApcCKO
R1094 T4786 T4783 punct +,ApcCKO
R1095 T4787 T4788 dep that,were
R1096 T4788 T4784 relcl were,mice
R1097 T4789 T4788 acomp heterozygous,were
R1098 T4790 T4789 prep for,heterozygous
R1099 T4791 T4792 det the,allele
R1100 T4792 T4790 pobj allele,for
R1101 T4793 T4792 amod final,allele
R1102 T4794 T4795 npadvmod Apc,conditional
R1103 T4795 T4792 amod conditional,allele
R1104 T4796 T4797 punct (,ApcCKO
R1105 T4797 T4795 parataxis ApcCKO,conditional
R1106 T4798 T4797 punct ),ApcCKO
R1107 T4799 T4800 dep that,removed
R1108 T4800 T4792 relcl removed,allele
R1109 T4801 T4802 det the,cassette
R1110 T4802 T4800 dobj cassette,removed
R1111 T4803 T4804 compound PGK,neomycin
R1112 T4804 T4802 compound neomycin,cassette
R1113 T4805 T4804 punct -,neomycin
R1114 T4806 T4800 cc and,removed
R1115 T4807 T4800 conj contains,removed
R1116 T4808 T4809 advmod only,sites
R1117 T4809 T4807 dobj sites,contains
R1118 T4810 T4809 det the,sites
R1119 T4811 T4809 compound loxP,sites
R1120 T4812 T4807 prep in,contains
R1121 T4813 T4814 det the,introns
R1122 T4814 T4812 pobj introns,in
R1123 T4815 T4814 acl flanking,introns
R1124 T4816 T4815 dobj exon,flanking
R1125 T4817 T4816 nummod 14,exon
R1126 T4818 T4775 punct .,crossed
R1127 T4820 T4821 aux To,assess
R1128 T4821 T4822 advcl assess,crossed
R1129 T4823 T4824 det the,effect
R1130 T4824 T4821 dobj effect,assess
R1131 T4825 T4824 prep of,effect
R1132 T4826 T4825 pcomp deleting,of
R1133 T4827 T4826 dobj exon,deleting
R1134 T4828 T4827 nummod 14,exon
R1135 T4829 T4821 prep in,assess
R1136 T4830 T4829 pobj mice,in
R1137 T4831 T4822 punct ", ",crossed
R1138 T4832 T4833 det both,lines
R1139 T4833 T4822 nsubjpass lines,crossed
R1140 T4834 T4833 prep of,lines
R1141 T4835 T4836 nmod ApcCKO,mice
R1142 T4836 T4834 pobj mice,of
R1143 T4837 T4835 punct /,ApcCKO
R1144 T4838 T4835 punct +,ApcCKO
R1145 T4839 T4822 auxpass were,crossed
R1146 T4840 T4822 prep with,crossed
R1147 T4841 T4842 det the,deleter
R1148 T4842 T4840 pobj deleter,with
R1149 T4843 T4842 compound Cre,deleter
R1150 T4844 T4842 punct -,deleter
R1151 T4845 T4846 aux to,generate
R1152 T4846 T4822 advcl generate,crossed
R1153 T4847 T4848 det the,line
R1154 T4848 T4846 dobj line,generate
R1155 T4849 T4850 compound germline,knockout
R1156 T4850 T4848 compound knockout,line
R1157 T4851 T4848 prep of,line
R1158 T4852 T4851 pobj Apc,of
R1159 T4853 T4848 punct ", ",line
R1160 T4854 T4848 acl designated,line
R1161 T4855 T4854 oprd ApcΔ580,designated
R1162 T4856 T4855 punct /,ApcΔ580
R1163 T4857 T4855 punct +,ApcΔ580
R1164 T4858 T4822 punct .,crossed
R1165 T4860 T4861 det The,allele
R1166 T4861 T4863 nsubj allele,lacks
R1167 T4862 T4861 amod mutant,allele
R1168 T4864 T4861 punct (,allele
R1169 T4865 T4861 appos ApcΔ580,allele
R1170 T4866 T4863 punct ),lacks
R1171 T4867 T4863 dobj exon,lacks
R1172 T4868 T4867 nummod 14,exon
R1173 T4869 T4870 punct (,1A
R1174 T4870 T4863 parataxis 1A,lacks
R1175 T4871 T4870 compound Figure,1A
R1176 T4872 T4870 punct ),1A
R1177 T4873 T4863 punct .,lacks
R1178 T4875 T4876 det The,transcript
R1179 T4876 T4877 nsubj transcript,results
R1180 T4878 T4876 prep from,transcript
R1181 T4879 T4878 pobj loss,from
R1182 T4880 T4879 prep of,loss
R1183 T4881 T4880 pobj exon,of
R1184 T4882 T4881 nummod 14,exon
R1185 T4883 T4877 prep in,results
R1186 T4884 T4885 det a,shift
R1187 T4885 T4883 pobj shift,in
R1188 T4886 T4885 prep in,shift
R1189 T4887 T4888 det the,frame
R1190 T4888 T4886 pobj frame,in
R1191 T4889 T4888 amod normal,frame
R1192 T4890 T4888 compound reading,frame
R1193 T4891 T4877 punct ", ",results
R1194 T4892 T4877 advcl resulting,results
R1195 T4893 T4892 prep in,resulting
R1196 T4894 T4895 det a,codon
R1197 T4895 T4893 pobj codon,in
R1198 T4896 T4895 amod premature,codon
R1199 T4897 T4898 compound chain,termination
R1200 T4898 T4895 compound termination,codon
R1201 T4899 T4900 dep which,result
R1202 T4900 T4895 relcl result,codon
R1203 T4901 T4900 punct ", ",result
R1204 T4902 T4903 mark if,utilized
R1205 T4903 T4900 advcl utilized,result
R1206 T4904 T4900 punct ", ",result
R1207 T4905 T4900 aux would,result
R1208 T4906 T4900 prep in,result
R1209 T4907 T4908 det a,polypeptide
R1210 T4908 T4906 pobj polypeptide,in
R1211 T4909 T4908 amod truncated,polypeptide
R1212 T4910 T4911 dep that,is
R1213 T4911 T4908 relcl is,polypeptide
R1214 T4912 T4913 nummod 605,aa
R1215 T4913 T4911 attr aa,is
R1216 T4914 T4913 prep in,aa
R1217 T4915 T4914 pobj length,in
R1218 T4916 T4913 punct ", ",aa
R1219 T4917 T4918 prep of,correspond
R1220 T4918 T4913 relcl correspond,aa
R1221 T4919 T4917 pobj which,of
R1222 T4920 T4921 det the,aa
R1223 T4921 T4918 nsubj aa,correspond
R1224 T4922 T4921 amod first,aa
R1225 T4923 T4921 nummod 580,aa
R1226 T4924 T4918 prep to,correspond
R1227 T4925 T4926 det the,protein
R1228 T4926 T4924 pobj protein,to
R1229 T4927 T4926 amod normal,protein
R1230 T4928 T4926 compound Apc,protein
R1231 T4929 T4877 punct .,results
R1232 T4931 T4932 compound Southern,blot
R1233 T4932 T4933 compound blot,analysis
R1234 T4933 T4934 nsubj analysis,confirmed
R1235 T4935 T4933 prep of,analysis
R1236 T4936 T4937 compound tail,DNA
R1237 T4937 T4935 pobj DNA,of
R1238 T4938 T4937 prep from,DNA
R1239 T4939 T4940 compound F1,offspring
R1240 T4940 T4938 pobj offspring,from
R1241 T4941 T4940 prep of,offspring
R1242 T4942 T4943 preconj both,ApcCKON
R1243 T4943 T4944 nmod ApcCKON,lines
R1244 T4944 T4941 pobj lines,of
R1245 T4945 T4943 cc and,ApcCKON
R1246 T4946 T4943 conj ApcΔ580,ApcCKON
R1247 T4947 T4948 det the,transmission
R1248 T4948 T4934 dobj transmission,confirmed
R1249 T4949 T4948 compound germline,transmission
R1250 T4950 T4948 prep of,transmission
R1251 T4951 T4952 amod modified,allele
R1252 T4952 T4950 pobj allele,of
R1253 T4953 T4952 compound Apc,allele
R1254 T4954 T4955 punct (,1B
R1255 T4955 T4934 parataxis 1B,confirmed
R1256 T4956 T4955 compound Figure,1B
R1257 T4957 T4955 punct ),1B
R1258 T4958 T4934 punct .,confirmed
R1259 T4960 T4961 nsubj Mice,are
R1260 T4962 T4963 dep that,are
R1261 T4963 T4960 relcl are,Mice
R1262 T4964 T4963 acomp heterozygous,are
R1263 T4965 T4964 prep for,heterozygous
R1264 T4966 T4967 compound ApcΔ580,mutation
R1265 T4967 T4965 pobj mutation,for
R1266 T4968 T4961 acomp viable,are
R1267 T4969 T4961 cc but,are
R1268 T4970 T4961 conj have,are
R1269 T4971 T4972 det a,lifespan
R1270 T4972 T4970 dobj lifespan,have
R1271 T4973 T4974 advmod significantly,reduced
R1272 T4974 T4972 amod reduced,lifespan
R1273 T4975 T4976 punct (,1C
R1274 T4976 T4970 parataxis 1C,have
R1275 T4977 T4976 compound Figure,1C
R1276 T4978 T4976 punct ),1C
R1277 T4979 T4961 punct .,are
R1278 T4981 T4982 det These,results
R1279 T4982 T4983 nsubj results,suggested
R1280 T4984 T4985 mark that,results
R1281 T4985 T4983 ccomp results,suggested
R1282 T4986 T4985 nsubj deletion,results
R1283 T4987 T4986 prep of,deletion
R1284 T4988 T4987 pobj exon,of
R1285 T4989 T4988 nummod 14,exon
R1286 T4990 T4985 advmod indeed,results
R1287 T4991 T4985 prep in,results
R1288 T4992 T4993 preconj either,loss
R1289 T4993 T4991 pobj loss,in
R1290 T4994 T4993 cc or,loss
R1291 T4995 T4996 amod abnormal,function
R1292 T4996 T4993 conj function,loss
R1293 T4997 T4993 prep of,loss
R1294 T4998 T4999 det the,product
R1295 T4999 T4997 pobj product,of
R1296 T5000 T5001 compound Apc,gene
R1297 T5001 T4999 compound gene,product
R1298 T5002 T4983 punct .,suggested
R1299 T5004 T5005 nmod ApcΔ580,mice
R1300 T5005 T5008 nsubj mice,have
R1301 T5006 T5004 punct /,ApcΔ580
R1302 T5007 T5004 punct +,ApcΔ580
R1303 T5009 T5010 amod median,survival
R1304 T5010 T5008 dobj survival,have
R1305 T5011 T5010 prep of,survival
R1306 T5012 T5013 nummod 5,mo
R1307 T5013 T5011 pobj mo,of
R1308 T5014 T5013 prep of,mo
R1309 T5015 T5014 pobj age,of
R1310 T5016 T5017 punct (,1C
R1311 T5017 T5010 parataxis 1C,survival
R1312 T5018 T5017 compound Figure,1C
R1313 T5019 T5017 punct ),1C
R1314 T5020 T5010 punct ", ",survival
R1315 T5021 T5010 prep with,survival
R1316 T5022 T5023 amod progressive,signs
R1317 T5023 T5021 pobj signs,with
R1318 T5024 T5023 prep of,signs
R1319 T5025 T5026 amod rectal,bleeding
R1320 T5026 T5024 pobj bleeding,of
R1321 T5131 T5129 nsubj mechanism,is
R1322 T5027 T5026 cc and,bleeding
R1323 T5028 T5026 conj anemia,bleeding
R1324 T5132 T5133 advmod most,likely
R1325 T5029 T5008 punct .,have
R1326 T5133 T5131 amod likely,mechanism
R1327 T5031 T5032 advcl Similar,had
R1328 T5033 T5031 prep to,Similar
R1329 T5134 T5131 prep of,mechanism
R1330 T5034 T5035 det the,results
R1331 T5035 T5033 pobj results,to
R1332 T5135 T5136 amod wild,type
R1333 T5036 T5035 acl reported,results
R1334 T5037 T5036 prep with,reported
R1335 T5038 T5039 det an,strain
R1336 T5136 T5138 compound type,inactivation
R1337 T5039 T5037 pobj strain,with
R1338 T5040 T5039 advmod independently,strain
R1339 T5041 T5039 amod generated,strain
R1340 T5137 T5136 punct -,type
R1341 T5042 T5043 npadvmod ApcΔ580,conditional
R1342 T5043 T5039 amod conditional,strain
R1343 T5044 T5042 punct /,ApcΔ580
R1344 T5138 T5134 pobj inactivation,of
R1345 T5045 T5042 punct +,ApcΔ580
R1346 T5046 T5039 compound mouse,strain
R1347 T5047 T5048 punct [,14
R1348 T5139 T5138 compound Apc,inactivation
R1349 T5048 T5036 parataxis 14,reported
R1350 T5049 T5048 punct ],14
R1351 T5050 T5032 punct ", ",had
R1352 T5140 T5129 prep by,is
R1353 T5051 T5052 nmod ApcΔ580,mice
R1354 T5052 T5032 nsubj mice,had
R1355 T5053 T5051 punct /,ApcΔ580
R1356 T5141 T5142 amod allelic,loss
R1357 T5054 T5051 punct +,ApcΔ580
R1358 T5055 T5056 amod more,100
R1359 T5056 T5058 nummod 100,tumors
R1360 T5142 T5140 pobj loss,by
R1361 T5057 T5056 quantmod than,100
R1362 T5143 T5116 punct .,showed
R1363 T5058 T5032 dobj tumors,had
R1364 T5059 T5060 punct (,37
R1365 T5060 T5056 parataxis 37,100
R1366 T5061 T5060 nummod 120,37
R1367 T5062 T5060 punct ±,37
R1368 T5145 T5146 det The,allele
R1369 T5063 T5060 punct ", ",37
R1370 T5064 T5065 nsubj n,11
R1371 T5065 T5060 ccomp 11,37
R1372 T5066 T5065 punct =,11
R1373 T5067 T5060 punct ),37
R1374 T5068 T5058 amod intestinal,tumors
R1375 T5069 T5032 prep at,had
R1376 T5070 T5071 det the,time
R1377 T5146 T5148 nsubj allele,had
R1378 T5071 T5069 pobj time,at
R1379 T5072 T5071 prep of,time
R1380 T5073 T5074 poss their,death
R1381 T5074 T5072 pobj death,of
R1382 T5147 T5146 amod mutant,allele
R1383 T5075 T5076 punct (,S1
R1384 T5076 T5032 parataxis S1,had
R1385 T5077 T5076 compound Figure,S1
R1386 T5149 T5150 aux to,maintained
R1387 T5078 T5076 punct ),S1
R1388 T5079 T5032 punct .,had
R1389 T5081 T5082 nsubj Inactivation,is
R1390 T5150 T5148 xcomp maintained,had
R1391 T5083 T5081 prep of,Inactivation
R1392 T5084 T5085 amod wild,type
R1393 T5151 T5150 auxpass be,maintained
R1394 T5085 T5087 compound type,Apc
R1395 T5086 T5085 punct -,type
R1396 T5087 T5083 pobj Apc,of
R1397 T5152 T5150 cc and,maintained
R1398 T5088 T5089 det an,prerequisite
R1399 T5089 T5082 attr prerequisite,is
R1400 T5090 T5089 amod important,prerequisite
R1401 T5153 T5150 conj transmitted,maintained
R1402 T5091 T5089 prep for,prerequisite
R1403 T5092 T5093 compound tumor,development
R1404 T5093 T5091 pobj development,for
R1405 T5154 T5153 prep through,transmitted
R1406 T5094 T5082 punct .,is
R1407 T5155 T5156 amod male,mice
R1408 T5096 T5097 nsubj We,analyzed
R1409 T5098 T5099 nummod 30,tumors
R1410 T5156 T5154 pobj mice,through
R1411 T5099 T5097 dobj tumors,analyzed
R1412 T5100 T5099 amod intestinal,tumors
R1413 T5157 T5153 punct ", ",transmitted
R1414 T5101 T5099 prep from,tumors
R1415 T5102 T5103 nmod ApcΔ580,mice
R1416 T5103 T5101 pobj mice,from
R1417 T5104 T5102 punct /,ApcΔ580
R1418 T5158 T5159 mark as,were
R1419 T5105 T5102 punct +,ApcΔ580
R1420 T5106 T5097 prep by,analyzed
R1421 T5159 T5153 advcl were,transmitted
R1422 T5160 T5161 nmod ApcΔ580,females
R1423 T5107 T5108 advmod in,vitro
R1424 T5108 T5109 amod vitro,transcription
R1425 T5109 T5106 pobj transcription,by
R1426 T5110 T5109 cc and,transcription
R1427 T5111 T5112 compound translation,assay
R1428 T5112 T5109 conj assay,transcription
R1429 T5161 T5159 nsubj females,were
R1430 T5113 T5097 punct ", ",analyzed
R1431 T5114 T5097 cc but,analyzed
R1432 T5115 T5116 nsubj none,showed
R1433 T5162 T5160 punct /,ApcΔ580
R1434 T5116 T5097 conj showed,analyzed
R1435 T5117 T5115 prep of,none
R1436 T5163 T5160 punct +,ApcΔ580
R1437 T5118 T5117 pobj them,of
R1438 T5119 T5120 amod truncated,products
R1439 T5120 T5116 dobj products,showed
R1440 T5164 T5159 advmod frequently,were
R1441 T5121 T5120 compound Apc,products
R1442 T5122 T5123 punct (,data
R1443 T5123 T5116 meta data,showed
R1444 T5165 T5159 neg not,were
R1445 T5124 T5123 amod unpublished,data
R1446 T5125 T5116 punct ),showed
R1447 T5126 T5116 punct ", ",showed
R1448 T5166 T5159 acomp healthy,were
R1449 T5127 T5116 advcl indicating,showed
R1450 T5128 T5129 mark that,is
R1451 T5129 T5127 ccomp is,indicating
R1452 T5167 T5166 advmod enough,healthy
R1453 T5130 T5131 det the,mechanism
R1454 T5168 T5169 aux to,nurse
R1455 T5169 T5166 xcomp nurse,healthy
R1456 T5170 T5169 advmod successfully,nurse
R1457 T5171 T5172 poss their,pups
R1458 T5237 T5238 amod wild,type
R1459 T5172 T5169 dobj pups,nurse
R1460 T5238 T5236 compound type,littermates
R1461 T5239 T5238 punct -,type
R1462 T5173 T5172 amod own,pups
R1463 T5240 T5241 punct (,1C
R1464 T5241 T5228 parataxis 1C,showing
R1465 T5242 T5241 compound Figure,1C
R1466 T5174 T5159 prep because,were
R1467 T5243 T5241 punct ),1C
R1468 T5244 T5217 punct .,are
R1469 T5175 T5174 pcomp of,because
R1470 T5246 T5247 nsubj We,tested
R1471 T5176 T5177 poss their,burden
R1472 T5248 T5249 mark whether,compliment
R1473 T5249 T5247 ccomp compliment,tested
R1474 T5177 T5174 pobj burden,because
R1475 T5250 T5251 poss our,allele
R1476 T5251 T5249 nsubj allele,compliment
R1477 T5252 T5251 compound ApcCKO,allele
R1478 T5253 T5249 aux can,compliment
R1479 T5254 T5255 det the,allele
R1480 T5255 T5249 dobj allele,compliment
R1481 T5256 T5257 amod wild,type
R1482 T5178 T5177 compound tumor,burden
R1483 T5257 T5255 compound type,allele
R1484 T5258 T5257 punct -,type
R1485 T5259 T5249 prep by,compliment
R1486 T5179 T5148 punct .,had
R1487 T5260 T5259 pcomp crossing,by
R1488 T5261 T5262 det the,female
R1489 T5262 T5260 dobj female,crossing
R1490 T5181 T5182 nmod ApcCKO,mice
R1491 T5263 T5264 compound ApcCKO,CKO
R1492 T5264 T5262 compound CKO,female
R1493 T5265 T5264 punct /,CKO
R1494 T5266 T5260 prep with,crossing
R1495 T5267 T5268 nmod ApcΔ580,mouse
R1496 T5268 T5266 pobj mouse,with
R1497 T5182 T5185 nsubjpass mice,intercrossed
R1498 T5269 T5267 punct /,ApcΔ580
R1499 T5270 T5267 punct +,ApcΔ580
R1500 T5271 T5268 amod male,mouse
R1501 T5183 T5181 punct /,ApcCKO
R1502 T5272 T5247 punct .,tested
R1503 T5184 T5181 punct +,ApcCKO
R1504 T5274 T5275 det The,offspring
R1505 T5275 T5280 nsubj offspring,were
R1506 T5276 T5275 amod resultant,offspring
R1507 T5186 T5185 auxpass were,intercrossed
R1508 T5277 T5278 compound ApcCKO,Δ580
R1509 T5278 T5275 compound Δ580,offspring
R1510 T5279 T5278 punct /,Δ580
R1511 T5187 T5188 aux to,generate
R1512 T5188 T5185 advcl generate,intercrossed
R1513 T5189 T5190 compound ApcCKO,CKO
R1514 T5281 T5280 acomp viable,were
R1515 T5190 T5192 compound CKO,offspring
R1516 T5191 T5190 punct /,CKO
R1517 T5282 T5281 cc and,viable
R1518 T5283 T5281 conj born,viable
R1519 T5192 T5188 dobj offspring,generate
R1520 T5284 T5283 prep in,born
R1521 T5285 T5286 det the,ratio
R1522 T5286 T5284 pobj ratio,in
R1523 T5193 T5185 punct .,intercrossed
R1524 T5287 T5286 amod Mendelian,ratio
R1525 T5288 T5280 punct ", ",were
R1526 T5289 T5280 advcl suggesting,were
R1527 T5195 T5196 advmod Approximately,one
R1528 T5290 T5291 mark that,have
R1529 T5291 T5289 ccomp have,suggesting
R1530 T5292 T5293 det the,presence
R1531 T5293 T5291 nsubj presence,have
R1532 T5294 T5293 prep of,presence
R1533 T5196 T5197 nsubj one,were
R1534 T5295 T5296 compound loxP,sites
R1535 T5296 T5294 pobj sites,of
R1536 T5297 T5293 prep in,presence
R1537 T5198 T5196 punct -,one
R1538 T5298 T5297 pobj introns,in
R1539 T5299 T5298 acl flanking,introns
R1540 T5300 T5299 dobj exon,flanking
R1541 T5301 T5300 nummod 14,exon
R1542 T5199 T5196 amod quarter,one
R1543 T5302 T5303 det no,effect
R1544 T5200 T5196 prep of,one
R1545 T5201 T5202 det the,offspring
R1546 T5202 T5200 pobj offspring,of
R1547 T5303 T5291 dobj effect,have
R1548 T5203 T5204 punct (,17
R1549 T5304 T5303 amod adverse,effect
R1550 T5305 T5303 prep on,effect
R1551 T5204 T5196 parataxis 17,one
R1552 T5306 T5307 det the,function
R1553 T5307 T5305 pobj function,on
R1554 T5308 T5307 prep of,function
R1555 T5205 T5204 prep of,17
R1556 T5309 T5310 det the,gene
R1557 T5310 T5308 pobj gene,of
R1558 T5311 T5310 compound Apc,gene
R1559 T5206 T5205 pobj 81,of
R1560 T5312 T5280 punct .,were
R1561 T5207 T5204 punct ),17
R1562 T5208 T5197 acomp homozygous,were
R1563 T5209 T5208 prep for,homozygous
R1564 T5210 T5211 det the,allele
R1565 T5211 T5209 pobj allele,for
R1566 T5212 T5211 compound ApcCKO,allele
R1567 T5213 T5197 punct .,were
R1568 T5215 T5216 det These,mice
R1569 T5216 T5217 nsubj mice,are
R1570 T5218 T5219 advmod as,as
R1571 T5219 T5216 cc as,mice
R1572 T5220 T5219 advmod well,as
R1573 T5221 T5222 amod heterozygous,mice
R1574 T5222 T5216 conj mice,mice
R1575 T5223 T5222 prep for,mice
R1576 T5224 T5225 compound ApcCKO,allele
R1577 T5225 T5223 pobj allele,for
R1578 T5226 T5217 acomp normal,are
R1579 T5227 T5217 punct ", ",are
R1580 T5228 T5217 advcl showing,are
R1581 T5229 T5230 det no,differences
R1582 T5230 T5228 dobj differences,showing
R1583 T5231 T5230 prep in,differences
R1584 T5232 T5233 poss their,survival
R1585 T5233 T5231 pobj survival,in
R1586 T5234 T5230 prep to,differences
R1587 T5235 T5236 det the,littermates
R1588 T5236 T5234 pobj littermates,to
R1595 T7674 T7675 npadvmod K14,Driven
R1596 T7675 T7677 amod Driven,Loss
R1597 T7676 T7675 punct -,Driven
R1598 T7677 T7678 nsubj Loss,Results
R1599 T7679 T7677 prep of,Loss
R1600 T7680 T7679 pobj Apc,of
R1601 T7681 T7678 prep in,Results
R1602 T7682 T7683 amod Severe,Retardation
R1603 T7683 T7681 pobj Retardation,in
R1604 T7684 T7683 compound Growth,Retardation
R1605 T7685 T7683 cc and,Retardation
R1606 T7686 T7687 amod Early,Lethality
R1607 T7687 T7683 conj Lethality,Retardation
R1608 T7689 T7690 aux To,introduce
R1609 T7690 T7691 advcl introduce,crossed
R1610 T7692 T7693 det the,mutation
R1611 T7693 T7690 dobj mutation,introduce
R1612 T7694 T7693 prep of,mutation
R1613 T7695 T7694 pobj Apc,of
R1614 T7696 T7690 prep into,introduce
R1615 T7697 T7696 pobj cells,into
R1616 T7698 T7697 acl expressing,cells
R1617 T7699 T7698 dobj K14,expressing
R1618 T7700 T7691 punct ", ",crossed
R1619 T7701 T7691 nsubj we,crossed
R1620 T7702 T7703 nmod WW6,mice
R1621 T7703 T7691 dobj mice,crossed
R1622 T7704 T7705 compound ES,cell
R1623 T7705 T7706 npadvmod cell,derived
R1624 T7706 T7703 amod derived,mice
R1625 T7707 T7706 punct –,derived
R1626 T7708 T7709 punct [,15
R1627 T7709 T7706 parataxis 15,derived
R1628 T7710 T7709 punct ],15
R1629 T7711 T7703 nmod ApcCKO,mice
R1630 T7712 T7711 punct /,ApcCKO
R1631 T7713 T7711 punct +,ApcCKO
R1632 T7714 T7703 prep with,mice
R1633 T7715 T7716 compound K14,cre
R1634 T7716 T7718 compound cre,mice
R1635 T7717 T7716 punct -,cre
R1636 T7718 T7714 pobj mice,with
R1637 T7719 T7718 compound recombinase,mice
R1638 T7720 T7703 prep in,mice
R1639 T7721 T7722 compound FVB,background
R1640 T7722 T7720 pobj background,in
R1641 T7723 T7724 punct [,16
R1642 T7724 T7691 parataxis 16,crossed
R1643 T7725 T7724 punct ],16
R1644 T7726 T7691 punct .,crossed
R1645 T7728 T7729 det The,mice
R1646 T7729 T7737 nsubj mice,were
R1647 T7730 T7731 nmod K14,cre
R1648 T7731 T7729 nmod cre,mice
R1649 T7732 T7731 punct -,cre
R1650 T7733 T7731 punct ;,cre
R1651 T7734 T7731 appos ApcCKO,cre
R1652 T7735 T7734 punct /,ApcCKO
R1653 T7736 T7734 punct +,ApcCKO
R1654 T7738 T7737 acomp normal,were
R1655 T7739 T7737 prep in,were
R1656 T7740 T7739 pobj appearance,in
R1657 T7741 T7737 cc and,were
R1658 T7742 T7737 conj were,were
R1659 T7743 T7742 acomp fertile,were
R1660 T7744 T7737 punct .,were
R1661 T7746 T7747 nmod K14,cre
R1662 T7747 T7749 nmod cre,males
R1663 T7748 T7747 punct -,cre
R1664 T7749 T7754 nsubjpass males,crossed
R1665 T7750 T7747 punct ;,cre
R1666 T7751 T7747 appos ApcCKO,cre
R1667 T7752 T7751 punct /,ApcCKO
R1668 T7753 T7751 punct +,ApcCKO
R1669 T7755 T7754 auxpass were,crossed
R1670 T7756 T7754 prep to,crossed
R1671 T7757 T7758 compound ApcCKO,CKO
R1672 T7758 T7760 compound CKO,females
R1673 T7759 T7758 punct /,CKO
R1674 T7760 T7756 pobj females,to
R1675 T7761 T7762 aux to,avoid
R1676 T7762 T7754 advcl avoid,crossed
R1677 T7763 T7764 det the,effect
R1678 T7764 T7762 dobj effect,avoid
R1679 T7765 T7764 amod potential,effect
R1680 T7766 T7764 compound deleter,effect
R1681 T7767 T7762 prep in,avoid
R1682 T7768 T7767 pobj oocytes,in
R1683 T7769 T7768 prep of,oocytes
R1684 T7770 T7771 compound K14,cre
R1685 T7771 T7773 npadvmod cre,positive
R1686 T7772 T7771 punct -,cre
R1687 T7773 T7775 amod positive,females
R1688 T7774 T7773 punct –,positive
R1689 T7775 T7769 pobj females,of
R1690 T7776 T7777 punct [,17
R1691 T7777 T7754 parataxis 17,crossed
R1692 T7778 T7777 punct ],17
R1693 T7779 T7754 punct .,crossed
R1694 T7781 T7782 det The,mice
R1695 T7782 T7783 nsubjpass mice,intercrossed
R1696 T7783 T7785 ccomp intercrossed,were
R1697 T7784 T7783 auxpass were,intercrossed
R1698 T7786 T7783 advmod thereafter,intercrossed
R1699 T7787 T7783 prep for,intercrossed
R1700 T7788 T7787 pobj maintenance,for
R1701 T7789 T7785 punct ;,were
R1702 T7790 T7785 advmod hence,were
R1703 T7791 T7785 punct ", ",were
R1704 T7792 T7793 det the,mice
R1705 T7793 T7785 nsubj mice,were
R1706 T7794 T7793 acl used,mice
R1707 T7795 T7794 prep for,used
R1708 T7796 T7795 pobj analysis,for
R1709 T7797 T7785 prep in,were
R1710 T7798 T7799 det a,background
R1711 T7799 T7797 pobj background,in
R1712 T7800 T7799 amod mixed,background
R1713 T7801 T7799 prep of,background
R1714 T7802 T7801 pobj FVB,of
R1715 T7803 T7802 punct ", ",FVB
R1716 T7804 T7805 nummod 129,S
R1717 T7805 T7802 conj S,FVB
R1718 T7806 T7805 punct /,S
R1719 T7807 T7805 punct ", ",S
R1720 T7808 T7805 cc and,S
R1721 T7809 T7805 conj C57BL,S
R1722 T7810 T7809 punct /,C57BL
R1723 T7811 T7809 nummod 6,C57BL
R1724 T7812 T7802 prep in,FVB
R1725 T7813 T7814 amod similar,proportions
R1726 T7814 T7812 pobj proportions,in
R1727 T7815 T7802 punct ", ",FVB
R1728 T7816 T7802 prep with,FVB
R1729 T7817 T7818 amod minimal,contribution
R1730 T7818 T7816 pobj contribution,with
R1731 T7819 T7818 prep of,contribution
R1732 T7820 T7819 pobj SJ,of
R1733 T7821 T7785 punct .,were
R1734 T7824 T7826 nsubj promoter,is
R1735 T7823 T7824 det The,promoter
R1736 T7825 T7824 compound K14,promoter
R1737 T7929 T7928 pobj crosses,from
R1738 T7827 T7828 det a,promoter
R1739 T7930 T7929 prep between,crosses
R1740 T7828 T7826 attr promoter,is
R1741 T7829 T7830 advmod commonly,used
R1742 T7830 T7828 amod used,promoter
R1743 T7831 T7832 amod epidermal,cell
R1744 T7832 T7828 compound cell,promoter
R1745 T7833 T7826 prep because,is
R1746 T7931 T7932 nmod K14,cre
R1747 T7834 T7833 pcomp of,because
R1748 T7835 T7836 poss its,expression
R1749 T7836 T7833 pobj expression,because
R1750 T7932 T7934 nmod cre,mice
R1751 T7837 T7836 prep by,expression
R1752 T7838 T7839 det the,cells
R1753 T7839 T7837 pobj cells,by
R1754 T7933 T7932 punct -,cre
R1755 T7840 T7841 advmod mitotically,active
R1756 T7841 T7839 amod active,cells
R1757 T7842 T7839 prep of,cells
R1758 T7934 T7930 pobj mice,between
R1759 T7843 T7844 det the,epidermis
R1760 T7844 T7842 pobj epidermis,of
R1761 T7845 T7844 cc and,epidermis
R1762 T7846 T7847 poss its,appendages
R1763 T7847 T7844 conj appendages,epidermis
R1764 T7848 T7836 prep in,expression
R1765 T7935 T7932 punct ;,cre
R1766 T7849 T7850 amod mature,skin
R1767 T7850 T7848 pobj skin,in
R1768 T7851 T7852 punct [,18
R1769 T7936 T7932 appos ApcCKO,cre
R1770 T7852 T7836 parataxis 18,expression
R1771 T7853 T7852 punct ],18
R1772 T7937 T7936 punct /,ApcCKO
R1773 T7938 T7936 punct +,ApcCKO
R1774 T7854 T7826 punct ", ",is
R1775 T7939 T7932 cc and,cre
R1776 T7855 T7826 cc but,is
R1777 T7856 T7857 advmod most,notably
R1778 T7857 T7858 advmod notably,is
R1779 T7858 T7826 conj is,is
R1780 T7940 T7941 compound ApcCKO,CKO
R1781 T7859 T7858 nsubj it,is
R1782 T7860 T7858 acomp active,is
R1783 T7941 T7932 conj CKO,cre
R1784 T7861 T7858 prep in,is
R1785 T7862 T7863 amod embryonic,ectoderm
R1786 T7942 T7941 punct /,CKO
R1787 T7863 T7861 pobj ectoderm,in
R1788 T7864 T7865 advmod as,early
R1789 T7865 T7858 advmod early,is
R1790 T7943 T7911 punct .,genotyped
R1791 T7866 T7865 prep as,early
R1792 T7867 T7868 det the,stage
R1793 T7868 T7866 pobj stage,as
R1794 T7945 T7946 det The,mice
R1795 T7869 T7870 amod single,layered
R1796 T7870 T7868 amod layered,stage
R1797 T7871 T7868 amod ectodermal,stage
R1798 T7872 T7868 prep of,stage
R1799 T7873 T7874 amod embryonic,day
R1800 T7874 T7872 pobj day,of
R1801 T7875 T7876 punct (,E
R1802 T7946 T7948 nsubjpass mice,born
R1803 T7876 T7874 parataxis E,day
R1804 T7877 T7876 punct ),E
R1805 T7878 T7874 nummod 9.5,day
R1806 T7879 T7880 punct [,19
R1807 T7947 T7946 amod mutant,mice
R1808 T7880 T7858 parataxis 19,is
R1809 T7881 T7880 punct ],19
R1810 T7949 T7946 prep of,mice
R1811 T7882 T7858 punct .,is
R1812 T7884 T7885 det A,expression
R1813 T7885 T7887 nsubjpass expression,found
R1814 T7886 T7885 amod restricted,expression
R1815 T7950 T7951 det the,genotype
R1816 T7888 T7885 prep of,expression
R1817 T7889 T7888 pobj K14,of
R1818 T7890 T7887 auxpass is,found
R1819 T7951 T7949 pobj genotype,of
R1820 T7891 T7887 advmod also,found
R1821 T7892 T7887 prep in,found
R1822 T7893 T7894 amod thymic,cells
R1823 T7952 T7953 compound K14,cre
R1824 T7894 T7892 pobj cells,in
R1825 T7895 T7894 amod epithelial,cells
R1826 T7953 T7951 appos cre,genotype
R1827 T7896 T7894 punct (,cells
R1828 T7897 T7894 appos TECs,cells
R1829 T7898 T7887 punct ),found
R1830 T7954 T7953 punct -,cre
R1831 T7899 T7887 prep in,found
R1832 T7900 T7901 det the,medulla
R1833 T7901 T7899 pobj medulla,in
R1834 T7902 T7901 prep of,medulla
R1835 T7955 T7953 punct ;,cre
R1836 T7903 T7904 amod normal,thymus
R1837 T7904 T7902 pobj thymus,of
R1838 T7905 T7906 punct [,20
R1839 T7956 T7957 compound ApcCKO,CKO
R1840 T7906 T7887 parataxis 20,found
R1841 T7907 T7906 punct ],20
R1842 T7908 T7887 punct .,found
R1843 T7957 T7953 appos CKO,cre
R1844 T7910 T7911 nsubj We,genotyped
R1845 T7958 T7957 punct /,CKO
R1846 T7912 T7913 quantmod a,458
R1847 T7913 T7916 nummod 458,pups
R1848 T7914 T7913 quantmod total,458
R1849 T7915 T7913 quantmod of,458
R1850 T7916 T7911 dobj pups,genotyped
R1851 T7959 T7960 punct (,mutant
R1852 T7917 T7918 punct (,old
R1853 T7918 T7916 parataxis old,pups
R1854 T7919 T7920 quantmod 8,10
R1855 T7920 T7922 nummod 10,d
R1856 T7960 T7946 parataxis mutant,mice
R1857 T7921 T7920 punct –,10
R1858 T7922 T7918 npadvmod d,old
R1859 T7923 T7918 punct ),old
R1860 T7961 T7960 advmod hereafter,mutant
R1861 T7924 T7916 prep from,pups
R1862 T7925 T7926 nummod 67,litters
R1863 T7926 T7924 pobj litters,from
R1864 T7962 T7960 punct ", ",mutant
R1865 T7927 T7926 acl resulting,litters
R1866 T7928 T7927 prep from,resulting
R1867 T7963 T7960 compound KA,mutant
R1868 T7964 T7960 punct ),mutant
R1869 T7965 T7948 auxpass were,born
R1870 T7966 T7948 punct ", ",born
R1871 T7967 T7948 cc but,born
R1872 T7968 T7969 det the,frequency
R1873 T8034 T8037 nummod 25,pups
R1874 T7969 T7971 nsubj frequency,was
R1875 T8035 T8034 quantmod total,25
R1876 T8036 T8034 quantmod of,25
R1877 T7970 T7969 amod observed,frequency
R1878 T8037 T8038 nsubjpass pups,born
R1879 T8039 T8038 auxpass were,born
R1880 T7971 T7948 conj was,born
R1881 T8040 T8038 prep from,born
R1882 T8041 T8042 nummod three,litters
R1883 T7972 T7969 prep of,frequency
R1884 T8042 T8040 pobj litters,from
R1885 T8043 T8042 punct ", ",litters
R1886 T8044 T8045 prep of,confirmed
R1887 T7973 T7974 compound KA,mutants
R1888 T8045 T8042 relcl confirmed,litters
R1889 T8046 T8044 pobj which,of
R1890 T8047 T8045 nsubjpass 7,confirmed
R1891 T7974 T7972 pobj mutants,of
R1892 T8048 T8049 punct (,%
R1893 T8049 T8047 parataxis %,7
R1894 T7975 T7976 advmod much,less
R1895 T8050 T8049 nummod 28,%
R1896 T8051 T8049 punct ),%
R1897 T8052 T8045 auxpass were,confirmed
R1898 T8053 T8054 aux to,be
R1899 T8054 T8045 xcomp be,confirmed
R1900 T8055 T8056 compound K14,cre
R1901 T8056 T8054 attr cre,be
R1902 T7976 T7971 acomp less,was
R1903 T8057 T8056 punct -,cre
R1904 T8058 T8056 punct ;,cre
R1905 T8059 T8060 compound ApcCKO,CKO
R1906 T7977 T7978 mark than,expected
R1907 T8060 T8056 appos CKO,cre
R1908 T8061 T8060 punct /,CKO
R1909 T8062 T8045 prep by,confirmed
R1910 T7978 T7976 advcl expected,less
R1911 T8063 T8062 pobj genotyping,by
R1912 T8064 T8045 punct ", ",confirmed
R1913 T7979 T7980 punct (,Table
R1914 T8065 T8045 advcl indicating,confirmed
R1915 T8066 T8067 mark that,born
R1916 T8067 T8065 ccomp born,indicating
R1917 T7980 T7976 parataxis Table,less
R1918 T8068 T8069 compound KA,mutants
R1919 T8069 T8067 nsubjpass mutants,born
R1920 T8070 T8067 auxpass were,born
R1921 T7981 T7980 dep 78,Table
R1922 T8071 T8067 prep in,born
R1923 T8072 T8073 det the,ratio
R1924 T8073 T8071 pobj ratio,in
R1925 T7982 T7981 prep of,78
R1926 T8074 T8073 amod expected,ratio
R1927 T8075 T8073 amod Mendelian,ratio
R1928 T7983 T7982 pobj 458,of
R1929 T8076 T8038 punct .,born
R1930 T8078 T8079 det The,pups
R1931 T7984 T7985 punct [,%
R1932 T8079 T8082 nsubjpass pups,nursed
R1933 T8080 T8079 nmod KA,pups
R1934 T8081 T8079 amod mutant,pups
R1935 T7985 T7981 parataxis %,78
R1936 T8083 T8082 auxpass were,nursed
R1937 T7986 T7985 nummod 17.0,%
R1938 T8084 T8082 advmod normally,nursed
R1939 T8085 T8082 punct ", ",nursed
R1940 T8086 T8082 cc and,nursed
R1941 T7987 T7985 punct ],%
R1942 T8087 T8088 expl there,was
R1943 T8088 T8082 conj was,nursed
R1944 T8089 T8088 attr milk,was
R1945 T7988 T7980 punct ;,Table
R1946 T8090 T8088 prep in,was
R1947 T8091 T8092 poss their,stomachs
R1948 T7989 T7990 nsubj p,analysis
R1949 T8092 T8090 pobj stomachs,in
R1950 T8093 T8088 prep during,was
R1951 T8094 T8095 det the,d
R1952 T8095 T8093 pobj d,during
R1953 T8096 T8095 amod first,d
R1954 T8097 T8095 nummod 2,d
R1955 T8098 T8097 cc or,2
R1956 T7990 T7980 ccomp analysis,Table
R1957 T8099 T8097 conj 3,2
R1958 T8100 T8095 prep after,d
R1959 T8101 T8100 pobj birth,after
R1960 T7991 T7990 punct <,analysis
R1961 T8102 T8082 punct ", ",nursed
R1962 T8103 T8082 cc but,nursed
R1963 T8104 T8105 nsubj they,failed
R1964 T7992 T7990 nummod 0.0005,analysis
R1965 T8105 T8082 conj failed,nursed
R1966 T7993 T7994 compound Chi,square
R1967 T8106 T8107 aux to,thrive
R1968 T8107 T8105 xcomp thrive,failed
R1969 T7994 T7990 compound square,analysis
R1970 T8108 T8109 punct (,Figure
R1971 T8109 T8107 parataxis Figure,thrive
R1972 T8110 T8109 nummod 2,Figure
R1973 T7995 T7994 punct -,square
R1974 T8111 T8109 punct ),Figure
R1975 T8112 T8105 punct .,failed
R1976 T7996 T7980 punct ", ",Table
R1977 T8114 T8115 prep By,were
R1978 T7997 T7980 nummod 1,Table
R1979 T8116 T8117 amod postnatal,day
R1980 T8117 T8114 pobj day,By
R1981 T7998 T7980 punct ),Table
R1982 T8118 T8117 punct (,day
R1983 T8119 T8117 appos P,day
R1984 T7999 T7971 punct .,was
R1985 T8120 T8117 punct ),day
R1986 T8121 T8117 appos 8,day
R1987 T8122 T8123 punct –,10
R1988 T8001 T8002 aux To,assess
R1989 T8123 T8121 prep 10,8
R1990 T8124 T8115 punct ", ",were
R1991 T8125 T8115 prep at,were
R1992 T8002 T8003 advcl assess,monitored
R1993 T8126 T8127 det the,time
R1994 T8127 T8125 pobj time,at
R1995 T8128 T8127 prep of,time
R1996 T8129 T8128 pobj genotyping,of
R1997 T8004 T8005 det the,basis
R1998 T8130 T8115 punct ", ",were
R1999 T8131 T8132 amod many,pups
R2000 T8005 T8002 dobj basis,assess
R2001 T8132 T8115 nsubj pups,were
R2002 T8133 T8132 nmod KA,pups
R2003 T8134 T8132 amod mutant,pups
R2004 T8135 T8136 advmod considerably,smaller
R2005 T8006 T8005 prep for,basis
R2006 T8136 T8115 acomp smaller,were
R2007 T8137 T8136 prep than,smaller
R2008 T8138 T8139 poss their,littermates
R2009 T8007 T8008 det the,lethality
R2010 T8139 T8137 pobj littermates,than
R2011 T8008 T8006 pobj lethality,for
R2012 T8009 T8008 amod neonatal,lethality
R2013 T8010 T8008 prep of,lethality
R2014 T8140 T8141 punct (,2B
R2015 T8141 T8115 parataxis 2B,were
R2016 T8011 T8012 compound KA,mutants
R2017 T8142 T8141 compound Figure,2B
R2018 T8143 T8144 punct –,2F
R2019 T8144 T8141 prep 2F,2B
R2020 T8012 T8010 pobj mutants,of
R2021 T8145 T8141 punct ),2B
R2022 T8146 T8115 cc and,were
R2023 T8013 T8003 punct ", ",monitored
R2024 T8147 T8148 nsubj some,died
R2025 T8148 T8115 conj died,were
R2026 T8149 T8148 aux have,died
R2027 T8014 T8003 nsubj we,monitored
R2028 T8150 T8148 prep at,died
R2029 T8151 T8150 cc or,at
R2030 T8015 T8016 nummod three,litters
R2031 T8152 T8153 amod prior,to
R2032 T8153 T8150 conj to,at
R2033 T8154 T8155 det this,age
R2034 T8016 T8003 dobj litters,monitored
R2035 T8155 T8153 pobj age,to
R2036 T8156 T8115 punct .,were
R2037 T8017 T8003 prep from,monitored
R2038 T8158 T8159 nsubj None,survived
R2039 T8018 T8017 pobj birth,from
R2040 T8160 T8158 prep of,None
R2041 T8161 T8162 compound KA,mutants
R2042 T8162 T8160 pobj mutants,of
R2043 T8019 T8003 prep to,monitored
R2044 T8163 T8159 prep to,survived
R2045 T8164 T8165 amod weaning,age
R2046 T8165 T8163 pobj age,to
R2047 T8020 T8019 pobj weaning,to
R2048 T8166 T8159 punct .,survived
R2049 T8021 T8003 prep by,monitored
R2050 T8168 T8169 det "Table 1 Genotype Distribution of Progeny from the Matings Figure 2 Postnatal Mortality and Stunted Growth in K14-cre; ApcCKO/CKO Mutant Mice Animals whose genotype is either heterozygous or homozygous for the wild-type Apc allele are referred to as normal (N); those whose genotype are K14-cre; ApcCKO/CKO and show the presence of K14-cre–recombined mutant Apc allele are called mutant (M). (A) Two P3 mutant mice, M1 and M2, and their normal littermates, showing size variation among mutants. (B) P8 mutant mouse (right) and a normal littermate. Note sparseness of hair coat and abnormal ears. (C–D) Vibrissae of whisker pads are short and oddly angled in a P12 mutant mouse (C), relative to control (D). Note the lack of incisors in the mutant. (E) A P17 mutant mouse (right) with its littermate. Its bare forehead, dorsal median line, and abnormal ears are evident. (F) Growth curve of mutants and normal littermates. Mutants exhibit stunted growth, which became more prominent as they aged, and weigh significantly less than littermates from P8 (p < 0.05). (G) Comparison of mutant and normal thymus from P3 mice. The mutant thymus (left) is dramatically smaller for its age compared to the normal littermate (right). The scale bar equals 1 mm. (H) Skeletal preparations of normal (left) and mutant (right), showing differences in development of both incisor (I) and molar (M) teeth. The",ability
R2051 T8169 T8170 nsubjpass ability,used
R2052 T8022 T8021 pcomp measuring,by
R2053 T8171 T8169 prep of,ability
R2054 T8172 T8173 amod whole,embryos
R2055 T8173 T8171 pobj embryos,of
R2056 T8174 T8175 aux to,exclude
R2057 T8175 T8169 acl exclude,ability
R2058 T8176 T8177 amod blue,dye
R2059 T8023 T8024 det the,weight
R2060 T8177 T8175 dobj dye,exclude
R2061 T8178 T8170 auxpass was,used
R2062 T8179 T8180 aux to,examine
R2063 T8024 T8022 dobj weight,measuring
R2064 T8180 T8170 advcl examine,used
R2065 T8181 T8182 det the,barrier
R2066 T8182 T8180 dobj barrier,examine
R2067 T8183 T8182 amod epidermal,barrier
R2068 T8025 T8024 compound body,weight
R2069 T8184 T8182 punct ", ",barrier
R2070 T8185 T8186 advmod normally,acquired
R2071 T8186 T8182 acl acquired,barrier
R2072 T8187 T8186 advcl beginning,acquired
R2073 T8026 T8024 prep of,weight
R2074 T8188 T8187 prep at,beginning
R2075 T8189 T8188 pobj E16,at
R2076 T8190 T8187 cc and,beginning
R2077 T8027 T8028 det each,pup
R2078 T8191 T8187 conj complete,beginning
R2079 T8028 T8026 pobj pup,of
R2080 T8192 T8191 prep by,complete
R2081 T8029 T8030 det every,day
R2082 T8193 T8192 pobj E18.5,by
R2083 T8194 T8195 punct [,21
R2084 T8195 T8186 parataxis 21,acquired
R2085 T8030 T8022 npadvmod day,measuring
R2086 T8196 T8195 punct ],21
R2087 T8197 T8170 punct .,used
R2088 T8031 T8003 punct .,monitored
R2089 T8199 T8200 nsubj Analyses,showed
R2090 T8201 T8199 prep of,Analyses
R2091 T8033 T8034 quantmod A,25
R2092 T8202 T8203 nmod E17.5,mutants
R2093 T8203 T8201 pobj mutants,of
R2094 T8204 T8205 punct –,E18.5
R2095 T8246 T8230 punct ", ",were
R2096 T8205 T8202 prep E18.5,E17.5
R2097 T8206 T8203 compound KA,mutants
R2098 T8207 T8208 mark that,were
R2099 T8208 T8200 ccomp were,showed
R2100 T8209 T8208 nsubj they,were
R2101 T8247 T8230 cc but,were
R2102 T8210 T8208 acomp able,were
R2103 T8211 T8212 aux to,exclude
R2104 T8248 T8249 det the,mutants
R2105 T8212 T8210 xcomp exclude,able
R2106 T8213 T8214 amod blue,dye
R2107 T8214 T8212 dobj dye,exclude
R2108 T8215 T8200 punct ", ",showed
R2109 T8216 T8200 advcl indicating,showed
R2110 T8249 T8250 nsubj mutants,showed
R2111 T8217 T8218 mark that,was
R2112 T8218 T8216 ccomp was,indicating
R2113 T8219 T8220 det the,barrier
R2114 T8250 T8230 conj showed,were
R2115 T8220 T8218 nsubj barrier,was
R2116 T8221 T8220 amod epidermal,barrier
R2117 T8222 T8218 acomp intact,was
R2118 T8251 T8252 det a,patch
R2119 T8223 T8224 punct (,S2
R2120 T8224 T8218 parataxis S2,was
R2121 T8225 T8224 compound Figure,S2
R2122 T8252 T8250 dobj patch,showed
R2123 T8226 T8224 punct ),S2
R2124 T8227 T8200 punct .,showed
R2125 T8253 T8252 prep of,patch
R2126 T8229 T8230 prep At,were
R2127 T8254 T8255 punct “,birthmark
R2128 T8231 T8232 det these,ages
R2129 T8232 T8229 pobj ages,At
R2130 T8233 T8232 amod embryonic,ages
R2131 T8255 T8253 pobj birthmark,of
R2132 T8234 T8230 punct ", ",were
R2133 T8235 T8230 expl there,were
R2134 T8236 T8237 det no,differences
R2135 T8256 T8255 punct ”,birthmark
R2136 T8237 T8230 attr differences,were
R2137 T8238 T8237 prep in,differences
R2138 T8239 T8238 pobj size,in
R2139 T8257 T8255 cc or,birthmark
R2140 T8240 T8237 prep between,differences
R2141 T8241 T8242 det the,mutants
R2142 T8242 T8240 pobj mutants,between
R2143 T8258 T8259 amod dark,pigmentation
R2144 T8243 T8242 cc and,mutants
R2145 T8244 T8245 poss their,littermates
R2146 T8245 T8242 conj littermates,mutants
R2147 T8259 T8255 conj pigmentation,birthmark
R2148 T8260 T8252 prep on,patch
R2149 T8261 T8262 poss their,foreheads
R2150 T8262 T8260 pobj foreheads,on
R2151 T8352 T8353 advmod phenotypically,normal
R2152 T8263 T8252 cc and,patch
R2153 T8353 T8351 amod normal,littermates
R2154 T8354 T8355 det a,coat
R2155 T8355 T8349 dobj coat,had
R2156 T8264 T8265 det a,line
R2157 T8356 T8355 amod smooth,coat
R2158 T8357 T8355 amod thin,coat
R2159 T8358 T8355 prep of,coat
R2160 T8359 T8358 pobj hair,of
R2161 T8360 T8361 punct (,2B
R2162 T8265 T8252 conj line,patch
R2163 T8361 T8349 parataxis 2B,had
R2164 T8362 T8361 compound Figure,2B
R2165 T8363 T8361 punct ),2B
R2166 T8364 T8336 punct .,were
R2167 T8266 T8265 amod dark,line
R2168 T8267 T8265 amod median,line
R2169 T8366 T8367 prep At,start
R2170 T8268 T8269 dep that,ran
R2171 T8368 T8369 det this,age
R2172 T8369 T8366 pobj age,At
R2173 T8269 T8265 relcl ran,line
R2174 T8370 T8367 punct ", ",start
R2175 T8371 T8372 nummod two,incisors
R2176 T8372 T8367 nsubj incisors,start
R2177 T8270 T8269 advmod caudally,ran
R2178 T8373 T8372 amod lower,incisors
R2179 T8374 T8375 aux to,erupt
R2180 T8375 T8367 xcomp erupt,start
R2181 T8271 T8269 prep from,ran
R2182 T8376 T8375 prep in,erupt
R2183 T8377 T8378 amod normal,littermates
R2184 T8272 T8271 pobj head,from
R2185 T8378 T8376 pobj littermates,in
R2186 T8379 T8367 cc and,start
R2187 T8273 T8269 prep to,ran
R2188 T8380 T8381 nsubj these,were
R2189 T8381 T8367 conj were,start
R2190 T8382 T8381 acomp absent,were
R2191 T8274 T8273 pobj tail,to
R2192 T8383 T8381 prep in,were
R2193 T8384 T8385 det the,mutants
R2194 T8385 T8383 pobj mutants,in
R2195 T8275 T8250 punct .,showed
R2196 T8386 T8385 compound KA,mutants
R2197 T8387 T8388 punct (,2C
R2198 T8277 T8278 poss Their,ears
R2199 T8388 T8381 parataxis 2C,were
R2200 T8389 T8388 compound Figure,2C
R2201 T8390 T8388 cc and,2C
R2202 T8391 T8388 conj 2D,2C
R2203 T8392 T8388 punct ),2C
R2204 T8278 T8280 nsubj ears,were
R2205 T8393 T8381 punct .,were
R2206 T8395 T8396 nsubj Animals,tended
R2207 T8279 T8278 amod external,ears
R2208 T8397 T8396 advmod also,tended
R2209 T8281 T8278 cc or,ears
R2210 T8398 T8399 aux to,be
R2211 T8399 T8396 xcomp be,tended
R2212 T8400 T8399 acomp smaller,be
R2213 T8401 T8396 cc and,tended
R2214 T8402 T8403 prep around,displayed
R2215 T8403 T8396 conj displayed,tended
R2216 T8404 T8402 pobj P10,around
R2217 T8405 T8406 punct –,P12
R2218 T8282 T8278 conj pinnae,ears
R2219 T8406 T8404 prep P12,P10
R2220 T8407 T8408 advmod abnormally,short
R2221 T8408 T8409 amod short,vibrissae
R2222 T8283 T8280 acomp shriveled,were
R2223 T8409 T8403 dobj vibrissae,displayed
R2224 T8410 T8408 cc and,short
R2225 T8411 T8408 conj misshapen,short
R2226 T8284 T8283 prep in,shriveled
R2227 T8412 T8409 cc and,vibrissae
R2228 T8413 T8414 amod short,hairs
R2229 T8414 T8409 conj hairs,vibrissae
R2230 T8285 T8284 pobj appearance,in
R2231 T8415 T8414 punct ", ",hairs
R2232 T8286 T8283 cc and,shriveled
R2233 T8287 T8283 conj pigmented,shriveled
R2234 T8416 T8414 amod shaggy,hairs
R2235 T8288 T8280 prep compared,were
R2236 T8417 T8414 compound pelage,hairs
R2237 T8418 T8419 punct (,2C
R2238 T8289 T8288 prep to,compared
R2239 T8419 T8403 parataxis 2C,displayed
R2240 T8420 T8419 compound Figure,2C
R2241 T8421 T8419 cc and,2C
R2242 T8290 T8289 pobj those,to
R2243 T8422 T8419 conj 2D,2C
R2244 T8423 T8419 punct ),2C
R2245 T8424 T8396 punct .,tended
R2246 T8291 T8290 prep of,those
R2247 T8426 T8427 nsubj Development,became
R2248 T8292 T8291 pobj littermates,of
R2249 T8428 T8426 prep of,Development
R2250 T8429 T8430 amod thick,ridges
R2251 T8293 T8280 punct .,were
R2252 T8430 T8428 pobj ridges,of
R2253 T8431 T8430 prep in,ridges
R2254 T8432 T8433 poss their,skin
R2255 T8295 T8296 amod External,characteristics
R2256 T8433 T8431 pobj skin,in
R2257 T8434 T8430 punct ", ",ridges
R2258 T8435 T8436 advmod particularly,around
R2259 T8436 T8430 prep around,ridges
R2260 T8296 T8297 nsubj characteristics,persisted
R2261 T8437 T8438 det the,ears
R2262 T8438 T8436 pobj ears,around
R2263 T8439 T8438 punct ", ",ears
R2264 T8440 T8438 conj eyelids,ears
R2265 T8441 T8440 punct ", ",eyelids
R2266 T8298 T8296 prep of,characteristics
R2267 T8442 T8440 conj forehead,eyelids
R2268 T8443 T8442 punct ", ",forehead
R2269 T8444 T8442 conj nose,forehead
R2270 T8445 T8444 punct ", ",nose
R2271 T8446 T8444 cc and,nose
R2272 T8447 T8444 conj paws,nose
R2273 T8299 T8300 compound KA,mutants
R2274 T8448 T8427 punct ", ",became
R2275 T8449 T8427 acomp noticeable,became
R2276 T8450 T8451 punct (,2E
R2277 T8300 T8298 pobj mutants,of
R2278 T8301 T8302 dep that,were
R2279 T8451 T8427 parataxis 2E,became
R2280 T8302 T8300 relcl were,mutants
R2281 T8452 T8451 compound Figure,2E
R2282 T8453 T8451 punct ),2E
R2283 T8303 T8302 acomp evident,were
R2284 T8454 T8427 punct .,became
R2285 T8304 T8302 prep at,were
R2286 T8456 T8457 det These,regions
R2287 T8457 T8458 nsubj regions,looked
R2288 T8305 T8304 pobj E18.5,at
R2289 T8306 T8297 prep after,persisted
R2290 T8307 T8306 pobj birth,after
R2291 T8459 T8458 acomp scaly,looked
R2292 T8460 T8458 punct ", ",looked
R2293 T8308 T8297 cc and,persisted
R2294 T8461 T8458 cc and,looked
R2295 T8309 T8297 conj became,persisted
R2296 T8462 T8463 det these,animals
R2297 T8463 T8464 nsubj animals,kept
R2298 T8464 T8458 conj kept,looked
R2299 T8310 T8311 advmod more,prominent
R2300 T8465 T8464 advmod hardly,kept
R2301 T8466 T8467 poss their,eyes
R2302 T8311 T8309 acomp prominent,became
R2303 T8467 T8464 dobj eyes,kept
R2304 T8468 T8464 oprd open,kept
R2305 T8469 T8464 punct .,kept
R2306 T8312 T8313 mark as,grew
R2307 T8471 T8472 prep In,started
R2308 T8313 T8309 advcl grew,became
R2309 T8472 T8490 ccomp started,were
R2310 T8473 T8471 pobj contrast,In
R2311 T8474 T8473 prep to,contrast
R2312 T8314 T8313 nsubj they,grew
R2313 T8475 T8476 det the,littermates
R2314 T8476 T8474 pobj littermates,to
R2315 T8477 T8476 amod normal,littermates
R2316 T8478 T8479 dep that,increased
R2317 T8479 T8476 relcl increased,littermates
R2318 T8480 T8479 advmod consistently,increased
R2319 T8315 T8316 punct (,2A
R2320 T8481 T8482 poss their,weight
R2321 T8482 T8479 dobj weight,increased
R2322 T8483 T8482 compound body,weight
R2323 T8316 T8309 parataxis 2A,became
R2324 T8484 T8479 prep with,increased
R2325 T8485 T8484 pobj age,with
R2326 T8317 T8316 compound Figure,2A
R2327 T8486 T8472 punct ", ",started
R2328 T8487 T8488 amod surviving,mutants
R2329 T8488 T8472 nsubj mutants,started
R2330 T8318 T8319 punct –,2F
R2331 T8489 T8488 compound KA,mutants
R2332 T8491 T8492 aux to,lose
R2333 T8319 T8316 prep 2F,2A
R2334 T8492 T8472 xcomp lose,started
R2335 T8493 T8492 dobj weight,lose
R2336 T8494 T8492 prep from,lose
R2337 T8320 T8316 punct ),2A
R2338 T8495 T8494 pobj P10,from
R2339 T8496 T8495 advmod onwards,P10
R2340 T8497 T8490 punct ;,were
R2341 T8321 T8297 punct .,persisted
R2342 T8498 T8490 prep by,were
R2343 T8499 T8498 pobj P16,by
R2344 T8500 T8501 punct –,P17
R2345 T8323 T8324 nsubjpass Growth,delayed
R2346 T8501 T8499 prep P17,P16
R2347 T8502 T8490 nsubj they,were
R2348 T8503 T8490 advmod all,were
R2349 T8504 T8490 acomp lethargic,were
R2350 T8325 T8323 prep of,Growth
R2351 T8505 T8490 punct ", ",were
R2352 T8506 T8490 cc and,were
R2353 T8507 T8508 nsubj none,survived
R2354 T8508 T8490 conj survived,were
R2355 T8326 T8327 compound pelage,hair
R2356 T8509 T8507 prep of,none
R2357 T8510 T8509 pobj them,of
R2358 T8511 T8508 prep to,survived
R2359 T8327 T8325 pobj hair,of
R2360 T8512 T8511 pobj weaning,to
R2361 T8513 T8514 punct (,2E
R2362 T8514 T8508 parataxis 2E,survived
R2363 T8328 T8324 auxpass was,delayed
R2364 T8515 T8514 compound Figure,2E
R2365 T8516 T8514 cc and,2E
R2366 T8517 T8514 conj 2F,2E
R2367 T8518 T8514 punct ),2E
R2368 T8519 T8490 punct .,were
R2369 T8329 T8324 advmod generally,delayed
R2370 T8521 T8522 prep At,were
R2371 T8330 T8324 prep in,delayed
R2372 T8523 T8524 det the,time
R2373 T8524 T8521 pobj time,At
R2374 T8525 T8524 prep of,time
R2375 T8331 T8332 det the,mutants
R2376 T8526 T8525 pobj autopsy,of
R2377 T8527 T8528 predet all,mutants
R2378 T8528 T8522 nsubj mutants,were
R2379 T8332 T8330 pobj mutants,in
R2380 T8529 T8528 det the,mutants
R2381 T8530 T8522 acomp toothless,were
R2382 T8531 T8522 punct ", ",were
R2383 T8532 T8522 prep without,were
R2384 T8333 T8324 punct .,delayed
R2385 T8533 T8532 pobj incisors,without
R2386 T8534 T8533 cc or,incisors
R2387 T8535 T8533 conj molars,incisors
R2388 T8335 T8336 prep At,were
R2389 T8536 T8522 punct ", ",were
R2390 T8537 T8522 cc and,were
R2391 T8337 T8338 advmod around,P8
R2392 T8538 T8539 poss their,stomachs
R2393 T8539 T8540 nsubj stomachs,were
R2394 T8540 T8522 conj were,were
R2395 T8338 T8335 pobj P8,At
R2396 T8541 T8540 advmod consistently,were
R2397 T8542 T8540 acomp small,were
R2398 T8543 T8540 cc and,were
R2399 T8339 T8336 punct ", ",were
R2400 T8544 T8540 conj had,were
R2401 T8545 T8546 det no,food
R2402 T8340 T8341 det the,mutants
R2403 T8546 T8544 dobj food,had
R2404 T8547 T8546 amod solid,food
R2405 T8341 T8336 nsubj mutants,were
R2406 T8548 T8544 punct ", ",had
R2407 T8549 T8544 prep unlike,had
R2408 T8550 T8551 poss their,littermates
R2409 T8342 T8341 compound KA,mutants
R2410 T8551 T8549 pobj littermates,unlike
R2411 T8552 T8553 npadvmod age,matched
R2412 T8553 T8551 amod matched,littermates
R2413 T8343 T8336 acomp hairless,were
R2414 T8554 T8553 punct -,matched
R2415 T8555 T8522 punct ", ",were
R2416 T8556 T8522 advcl suggesting,were
R2417 T8344 T8336 cc and,were
R2418 T8557 T8558 mark that,be
R2419 T8558 T8556 ccomp be,suggesting
R2420 T8559 T8560 det the,loss
R2421 T8560 T8558 nsubj loss,be
R2422 T8561 T8560 amod observed,loss
R2423 T8345 T8336 conj had,were
R2424 T8562 T8560 compound weight,loss
R2425 T8563 T8558 aux could,be
R2426 T8346 T8347 amod wrinkled,skin
R2427 T8347 T8345 dobj skin,had
R2428 T8564 T8565 det the,result
R2429 T8348 T8349 mark while,had
R2430 T8565 T8558 attr result,be
R2431 T8349 T8336 advcl had,were
R2432 T8566 T8565 prep of,result
R2433 T8567 T8566 pobj failure,of
R2434 T8568 T8569 aux to,ingest
R2435 T8569 T8567 acl ingest,failure
R2436 T8350 T8351 poss their,littermates
R2437 T8570 T8571 amod solid,food
R2438 T8571 T8569 dobj food,ingest
R2439 T8572 T8573 punct (,2F
R2440 T8351 T8349 nsubj littermates,had
R2441 T8573 T8558 parataxis 2F,be
R2442 T8574 T8573 compound Figure,2F
R2443 T8575 T8573 punct ),2F
R2444 T8670 T8669 punct -,mediated
R2445 T8576 T8522 punct .,were
R2446 T8578 T8579 advmod Interestingly,varied
R2447 T8671 T8667 pobj deletion,of
R2448 T8580 T8579 punct ", ",varied
R2449 T8581 T8579 nsubj changes,varied
R2450 T8582 T8581 prep in,changes
R2451 T8672 T8671 compound Apc,deletion
R2452 T8583 T8584 compound body,weights
R2453 T8584 T8582 pobj weights,in
R2454 T8585 T8584 cc and,weights
R2455 T8673 T8655 punct .,suggests
R2456 T8586 T8584 conj timing,weights
R2457 T8587 T8586 prep of,timing
R2458 T8588 T8589 compound hair,growth
R2459 T8675 T8676 nsubj It,is
R2460 T8589 T8587 pobj growth,of
R2461 T8590 T8579 advmod considerably,varied
R2462 T8591 T8579 prep among,varied
R2463 T8592 T8593 amod mutant,pups
R2464 T8677 T8676 acomp possible,is
R2465 T8593 T8591 pobj pups,among
R2466 T8594 T8595 advmod even,were
R2467 T8595 T8579 advcl were,varied
R2468 T8596 T8595 mark if,were
R2469 T8678 T8679 mark that,has
R2470 T8597 T8595 nsubj they,were
R2471 T8598 T8595 prep from,were
R2472 T8599 T8600 det the,litter
R2473 T8600 T8598 pobj litter,from
R2474 T8601 T8600 amod same,litter
R2475 T8602 T8595 punct ", ",were
R2476 T8679 T8676 ccomp has,is
R2477 T8603 T8604 mark whereas,tended
R2478 T8604 T8595 advcl tended,were
R2479 T8605 T8604 nsubj those,tended
R2480 T8680 T8681 det the,background
R2481 T8606 T8605 prep of,those
R2482 T8607 T8608 advmod phenotypically,normal
R2483 T8681 T8679 nsubj background,has
R2484 T8608 T8609 amod normal,littermates
R2485 T8609 T8606 pobj littermates,of
R2486 T8610 T8611 aux to,be
R2487 T8682 T8681 amod genetic,background
R2488 T8611 T8604 xcomp be,tended
R2489 T8612 T8611 acomp similar,be
R2490 T8613 T8579 punct .,varied
R2491 T8683 T8684 det a,role
R2492 T8615 T8616 det This,difference
R2493 T8616 T8617 nsubjpass difference,reflected
R2494 T8684 T8679 dobj role,has
R2495 T8617 T8620 ccomp reflected,survived
R2496 T8618 T8617 auxpass was,reflected
R2497 T8685 T8686 aux to,play
R2498 T8619 T8617 advmod also,reflected
R2499 T8621 T8617 prep in,reflected
R2500 T8686 T8684 advcl play,role
R2501 T8687 T8686 prep in,play
R2502 T8622 T8623 det the,variation
R2503 T8623 T8621 pobj variation,in
R2504 T8688 T8689 det this,variability
R2505 T8624 T8623 prep in,variation
R2506 T8625 T8624 pobj timing,in
R2507 T8626 T8625 prep of,timing
R2508 T8689 T8687 pobj variability,in
R2509 T8627 T8626 pobj death,of
R2510 T8628 T8623 prep in,variation
R2511 T8629 T8628 pobj mutants,in
R2512 T8630 T8620 punct : ,survived
R2513 T8690 T8676 punct .,is
R2514 T8631 T8632 det some,pups
R2515 T8632 T8634 nsubjpass pups,born
R2516 T8692 T8693 amod Gross,examination
R2517 T8633 T8632 amod mutant,pups
R2518 T8634 T8620 ccomp born,survived
R2519 T8635 T8634 auxpass were,born
R2520 T8636 T8634 advcl alive,born
R2521 T8693 T8694 nsubj examination,showed
R2522 T8637 T8634 cc but,born
R2523 T8638 T8634 conj died,born
R2524 T8639 T8638 prep within,died
R2525 T8640 T8641 nummod a,day
R2526 T8641 T8639 pobj day,within
R2527 T8642 T8643 cc or,two
R2528 T8643 T8641 nummod two,day
R2529 T8695 T8693 prep of,examination
R2530 T8644 T8620 punct ", ",survived
R2531 T8645 T8620 nsubj some,survived
R2532 T8646 T8620 advmod close,survived
R2533 T8647 T8646 prep to,close
R2534 T8696 T8697 amod internal,organs
R2535 T8648 T8649 det the,age
R2536 T8649 T8647 pobj age,to
R2537 T8650 T8649 amod weaning,age
R2538 T8697 T8695 pobj organs,of
R2539 T8651 T8620 punct .,survived
R2540 T8698 T8694 advmod also,showed
R2541 T8653 T8654 det This,variability
R2542 T8654 T8655 nsubj variability,suggests
R2543 T8699 T8700 mark that,were
R2544 T8656 T8654 prep of,variability
R2545 T8657 T8658 det the,phenotypes
R2546 T8658 T8656 pobj phenotypes,of
R2547 T8659 T8658 amod mutant,phenotypes
R2548 T8700 T8694 ccomp were,showed
R2549 T8660 T8661 amod possible,variation
R2550 T8661 T8655 dobj variation,suggests
R2551 T8701 T8702 det the,mutants
R2552 T8662 T8661 prep in,variation
R2553 T8663 T8664 det the,timing
R2554 T8664 T8662 pobj timing,in
R2555 T8665 T8664 cc and,timing
R2556 T8702 T8703 poss mutants,thymi
R2557 T8666 T8664 conj efficiency,timing
R2558 T8667 T8664 prep of,timing
R2559 T8668 T8669 npadvmod cre,mediated
R2560 T8703 T8700 nsubj thymi,were
R2561 T8669 T8671 amod mediated,deletion
R2562 T8704 T8702 case ',mutants
R2563 T8705 T8706 advmod consistently,inconspicuous
R2564 T8776 T8774 dobj specimens,preparing
R2565 T8706 T8700 acomp inconspicuous,were
R2566 T8777 T8776 prep of,specimens
R2567 T8778 T8779 nmod P16,mice
R2568 T8779 T8777 pobj mice,of
R2569 T8707 T8700 cc and,were
R2570 T8780 T8781 punct –,P17
R2571 T8781 T8778 prep P17,P16
R2572 T8782 T8779 acl stained,mice
R2573 T8783 T8782 prep with,stained
R2574 T8784 T8785 compound Alizarin,red
R2575 T8785 T8783 pobj red,with
R2576 T8786 T8766 punct .,examined
R2577 T8708 T8700 conj were,were
R2578 T8788 T8789 det No,differences
R2579 T8789 T8790 nsubjpass differences,detected
R2580 T8709 T8710 advmod very,small
R2581 T8791 T8789 prep between,differences
R2582 T8792 T8793 det the,mice
R2583 T8710 T8708 acomp small,were
R2584 T8711 T8710 prep for,small
R2585 T8793 T8791 pobj mice,between
R2586 T8712 T8713 poss their,age
R2587 T8794 T8793 amod normal,mice
R2588 T8795 T8794 cc and,normal
R2589 T8796 T8797 npadvmod KA,mutant
R2590 T8713 T8711 pobj age,for
R2591 T8797 T8794 conj mutant,normal
R2592 T8798 T8789 prep in,differences
R2593 T8799 T8800 det the,bone
R2594 T8714 T8700 punct ", ",were
R2595 T8800 T8798 pobj bone,in
R2596 T8801 T8800 amod mandibular,bone
R2597 T8802 T8790 aux can,detected
R2598 T8715 T8716 mark whereas,were
R2599 T8803 T8790 auxpass be,detected
R2600 T8804 T8790 punct ", ",detected
R2601 T8716 T8700 advcl were,were
R2602 T8805 T8790 cc but,detected
R2603 T8717 T8716 nsubj those,were
R2604 T8806 T8807 det the,mice
R2605 T8807 T8809 nsubj mice,lacked
R2606 T8718 T8717 prep of,those
R2607 T8719 T8720 poss their,littermates
R2608 T8808 T8807 amod mutant,mice
R2609 T8720 T8718 pobj littermates,of
R2610 T8721 T8722 advmod very,prominent
R2611 T8722 T8716 acomp prominent,were
R2612 T8809 T8790 conj lacked,detected
R2613 T8810 T8809 cc or,lacked
R2614 T8723 T8722 prep in,prominent
R2615 T8811 T8809 conj had,lacked
R2616 T8812 T8813 amod underdeveloped,set
R2617 T8813 T8811 dative set,had
R2618 T8724 T8723 pobj size,in
R2619 T8814 T8813 prep of,set
R2620 T8815 T8816 amod maxillary,incisors
R2621 T8816 T8811 dobj incisors,had
R2622 T8725 T8726 punct (,2G
R2623 T8817 T8816 cc and,incisors
R2624 T8818 T8816 conj molars,incisors
R2625 T8819 T8820 punct (,2H
R2626 T8820 T8811 parataxis 2H,had
R2627 T8821 T8820 compound Figure,2H
R2628 T8822 T8820 punct ),2H
R2629 T8726 T8716 parataxis 2G,were
R2630 T8823 T8809 punct .,lacked
R2631 T8825 T8826 nsubj We,detected
R2632 T8727 T8726 compound Figure,2G
R2633 T8827 T8828 det no,abnormalities
R2634 T8828 T8826 dobj abnormalities,detected
R2635 T8728 T8726 punct ),2G
R2636 T8829 T8828 amod other,abnormalities
R2637 T8830 T8828 amod major,abnormalities
R2638 T8729 T8694 punct .,showed
R2639 T8831 T8828 amod skeletal,abnormalities
R2640 T8832 T8826 punct .,detected
R2641 T8731 T8732 det This,difference
R2642 T8732 T8733 nsubj difference,was
R2643 T8734 T8733 acomp evident,was
R2644 T8735 T8736 advmod as,early
R2645 T8736 T8733 advmod early,was
R2646 T8737 T8736 prep as,early
R2647 T8738 T8737 pobj P3,as
R2648 T8739 T8733 punct .,was
R2649 T8741 T8742 advmod Quite,frequently
R2650 T8742 T8743 advmod frequently,contained
R2651 T8744 T8745 amod mutant,thymi
R2652 T8745 T8743 nsubj thymi,contained
R2653 T8746 T8745 prep in,thymi
R2654 T8747 T8748 nmod P12,mice
R2655 T8748 T8746 pobj mice,in
R2656 T8749 T8750 punct –,P17
R2657 T8750 T8747 prep P17,P12
R2658 T8751 T8748 amod mutant,mice
R2659 T8752 T8743 advmod also,contained
R2660 T8753 T8754 amod black,deposits
R2661 T8754 T8743 dobj deposits,contained
R2662 T8755 T8743 prep within,contained
R2663 T8756 T8757 det the,tissue
R2664 T8757 T8755 pobj tissue,within
R2665 T8758 T8759 punct (,data
R2666 T8759 T8743 meta data,contained
R2667 T8760 T8759 amod unpublished,data
R2668 T8761 T8759 punct ),data
R2669 T8762 T8743 punct .,contained
R2670 T8764 T8765 amod Mutant,mice
R2671 T8765 T8766 nsubjpass mice,examined
R2672 T8767 T8766 auxpass were,examined
R2673 T8768 T8766 advmod also,examined
R2674 T8769 T8766 prep for,examined
R2675 T8770 T8771 det any,abnormalities
R2676 T8771 T8769 pobj abnormalities,for
R2677 T8772 T8771 amod skeletal,abnormalities
R2678 T8773 T8766 prep by,examined
R2679 T8774 T8773 pcomp preparing,by
R2680 T8775 T8776 amod skeletal,specimens
R2681 T9607 T9608 npadvmod Genotype,Specific
R2682 T9608 T9613 amod Specific,Expression
R2683 T9609 T9607 punct -,Genotype
R2684 T9610 T9607 cc and,Genotype
R2685 T9611 T9607 conj Tissue,Genotype
R2686 T9612 T9608 punct -,Specific
R2687 T9614 T9613 prep of,Expression
R2688 T9615 T9616 det the,Transcripts
R2689 T9616 T9614 pobj Transcripts,of
R2690 T9617 T9618 amod Truncated,Apc
R2691 T9618 T9616 compound Apc,Transcripts
R2692 T9620 T9621 aux To,assess
R2693 T9621 T9622 advcl assess,screened
R2694 T9623 T9624 det the,effects
R2695 T9624 T9621 dobj effects,assess
R2696 T9625 T9624 amod molecular,effects
R2697 T9626 T9624 prep of,effects
R2698 T9627 T9628 det the,recombination
R2699 T9628 T9626 pobj recombination,of
R2700 T9629 T9630 compound K14,cre
R2701 T9630 T9632 npadvmod cre,mediated
R2702 T9631 T9630 punct -,cre
R2703 T9632 T9628 amod mediated,recombination
R2704 T9633 T9632 punct –,mediated
R2705 T9634 T9622 punct ", ",screened
R2706 T9635 T9622 nsubj we,screened
R2707 T9636 T9622 prep for,screened
R2708 T9637 T9638 det the,presence
R2709 T9638 T9636 pobj presence,for
R2710 T9639 T9638 prep of,presence
R2711 T9640 T9641 amod deleted,Apc
R2712 T9641 T9642 nmod Apc,alleles
R2713 T9642 T9639 pobj alleles,of
R2714 T9643 T9641 punct (,Apc
R2715 T9644 T9641 appos ApcΔ580,Apc
R2716 T9645 T9642 punct ),alleles
R2717 T9646 T9622 punct .,screened
R2718 T9648 T9649 amod Genomic,DNA
R2719 T9649 T9650 nsubjpass DNA,extracted
R2720 T9651 T9650 auxpass was,extracted
R2721 T9652 T9650 prep from,extracted
R2722 T9653 T9652 pobj liver,from
R2723 T9654 T9653 punct ", ",liver
R2724 T9655 T9653 conj thymus,liver
R2725 T9656 T9655 punct ", ",thymus
R2726 T9657 T9655 cc and,thymus
R2727 T9658 T9655 conj skin,thymus
R2728 T9659 T9653 prep from,liver
R2729 T9660 T9661 det all,genotypes
R2730 T9661 T9659 pobj genotypes,from
R2731 T9662 T9661 nummod 4,genotypes
R2732 T9663 T9661 amod possible,genotypes
R2733 T9664 T9661 punct : ,genotypes
R2734 T9665 T9666 compound K14,cre
R2735 T9666 T9661 appos cre,genotypes
R2736 T9667 T9666 punct -,cre
R2737 T9668 T9666 punct ;,cre
R2738 T9669 T9670 compound ApcCKO,CKO
R2739 T9670 T9666 appos CKO,cre
R2740 T9671 T9670 punct /,CKO
R2741 T9672 T9666 punct ", ",cre
R2742 T9673 T9674 compound K14,cre
R2743 T9674 T9666 conj cre,cre
R2744 T9675 T9674 punct -,cre
R2745 T9676 T9674 punct ;,cre
R2746 T9677 T9674 appos ApcCKO,cre
R2747 T9678 T9677 punct /,ApcCKO
R2748 T9679 T9677 punct +,ApcCKO
R2749 T9680 T9674 punct ", ",cre
R2750 T9681 T9682 compound ApcCKO,CKO
R2751 T9682 T9674 conj CKO,cre
R2752 T9683 T9682 punct /,CKO
R2753 T9684 T9682 punct ", ",CKO
R2754 T9685 T9682 cc and,CKO
R2755 T9686 T9682 conj ApcCKO,CKO
R2756 T9687 T9686 punct /,ApcCKO
R2757 T9688 T9686 punct +,ApcCKO
R2758 T9689 T9650 punct .,extracted
R2759 T9691 T9692 nsubj Genotyping,showed
R2760 T9693 T9691 prep on,Genotyping
R2761 T9694 T9695 amod genomic,DNA
R2762 T9695 T9693 pobj DNA,on
R2763 T9696 T9695 prep from,DNA
R2764 T9697 T9698 det these,tissues
R2765 T9698 T9696 pobj tissues,from
R2766 T9699 T9700 mark that,detected
R2767 T9700 T9692 ccomp detected,showed
R2768 T9701 T9702 det the,allele
R2769 T9702 T9700 nsubjpass allele,detected
R2770 T9703 T9702 compound ApcΔ580,allele
R2771 T9704 T9705 punct (,product
R2772 T9705 T9702 parataxis product,allele
R2773 T9706 T9707 nummod 500,bp
R2774 T9707 T9705 compound bp,product
R2775 T9708 T9707 punct -,bp
R2776 T9709 T9705 punct ),product
R2777 T9710 T9700 auxpass was,detected
R2778 T9711 T9712 advmod only,from
R2779 T9712 T9700 prep from,detected
R2780 T9713 T9714 det the,skin
R2781 T9714 T9712 pobj skin,from
R2782 T9715 T9714 cc and,skin
R2783 T9716 T9714 conj thymus,skin
R2784 T9717 T9714 prep of,skin
R2785 T9718 T9719 det the,mice
R2786 T9719 T9717 pobj mice,of
R2787 T9720 T9721 compound K14,cre
R2788 T9721 T9723 npadvmod cre,positive
R2789 T9722 T9721 punct -,cre
R2790 T9723 T9719 amod positive,mice
R2791 T9724 T9723 punct –,positive
R2792 T9725 T9692 punct .,showed
R2793 T9727 T9728 det The,presence
R2794 T9728 T9729 nsubj presence,was
R2795 T9730 T9728 prep of,presence
R2796 T9731 T9732 amod mutant,allele
R2797 T9732 T9730 pobj allele,of
R2798 T9733 T9732 compound Apc,allele
R2799 T9734 T9732 prep in,allele
R2800 T9735 T9736 det the,thymus
R2801 T9736 T9734 pobj thymus,in
R2802 T9737 T9736 prep of,thymus
R2803 T9738 T9739 nmod K14,cre
R2804 T9739 T9741 nmod cre,mice
R2805 T9740 T9739 punct -,cre
R2806 T9741 T9737 pobj mice,of
R2807 T9742 T9739 punct ;,cre
R2808 T9743 T9739 appos ApcCKO,cre
R2809 T9744 T9743 punct /,ApcCKO
R2810 T9745 T9743 punct +,ApcCKO
R2811 T9746 T9729 advmod consistently,was
R2812 T9747 T9748 advmod much,less
R2813 T9748 T9729 acomp less,was
R2814 T9749 T9748 prep than,less
R2815 T9750 T9751 det the,DNA
R2816 T9751 T9749 pobj DNA,than
R2817 T9752 T9751 prep from,DNA
R2818 T9753 T9754 det the,skin
R2819 T9754 T9752 pobj skin,from
R2820 T9755 T9754 prep of,skin
R2821 T9756 T9757 det the,animal
R2822 T9757 T9755 pobj animal,of
R2823 T9758 T9757 amod same,animal
R2824 T9759 T9751 cc or,DNA
R2825 T9760 T9761 amod other,tissues
R2826 T9761 T9751 conj tissues,DNA
R2827 T9762 T9761 prep from,tissues
R2828 T9763 T9764 det the,mutants
R2829 T9764 T9762 pobj mutants,from
R2830 T9765 T9764 compound KA,mutants
R2831 T9766 T9729 punct .,was
R2832 T9768 T9769 prep In,detected
R2833 T9770 T9768 pobj addition,In
R2834 T9771 T9769 punct ", ",detected
R2835 T9772 T9773 det this,product
R2836 T9773 T9769 nsubjpass product,detected
R2837 T9774 T9769 auxpass was,detected
R2838 T9775 T9769 neg not,detected
R2839 T9776 T9777 advmod at,all
R2840 T9777 T9769 advmod all,detected
R2841 T9778 T9769 prep in,detected
R2842 T9779 T9780 preconj either,liver
R2843 T9780 T9778 pobj liver,in
R2844 T9781 T9780 det the,liver
R2845 T9782 T9780 prep of,liver
R2846 T9783 T9784 compound K14,cre
R2847 T9784 T9786 npadvmod cre,positive
R2848 T9785 T9784 punct -,cre
R2849 T9786 T9782 amod positive,of
R2850 T9787 T9786 punct –,positive
R2851 T9788 T9778 cc or,in
R2852 T9789 T9778 conj in,in
R2853 T9790 T9789 pobj any,in
R2854 T9791 T9790 prep of,any
R2855 T9792 T9793 det the,negative
R2856 T9793 T9791 pobj negative,of
R2857 T9794 T9795 compound K14,cre
R2858 T9795 T9793 npadvmod cre,negative
R2859 T9796 T9795 punct -,cre
R2860 T9797 T9793 punct –,negative
R2861 T9798 T9799 compound mouse,samples
R2862 T9799 T9789 pobj samples,in
R2863 T9800 T9799 compound tissues,samples
R2864 T9801 T9769 punct ", ",detected
R2865 T9802 T9769 advcl establishing,detected
R2866 T9803 T9804 mark that,taken
R2867 T9804 T9802 ccomp taken,establishing
R2868 T9805 T9806 npadvmod Cre,mediated
R2869 T9806 T9808 amod mediated,recombination
R2870 T9807 T9806 punct -,mediated
R2871 T9808 T9804 nsubj recombination,taken
R2872 T9809 T9804 aux has,taken
R2873 T9810 T9804 dobj place,taken
R2874 T9811 T9804 prep in,taken
R2875 T9812 T9813 det the,manner
R2876 T9813 T9811 pobj manner,in
R2877 T9814 T9815 npadvmod tissue,specific
R2878 T9815 T9813 amod specific,manner
R2879 T9816 T9815 punct -,specific
R2880 T9817 T9804 prep in,taken
R2881 T9818 T9819 det the,mice
R2882 T9819 T9817 pobj mice,in
R2883 T9820 T9821 dep that,inherited
R2884 T9821 T9819 relcl inherited,mice
R2885 T9822 T9823 compound K14,cre
R2886 T9823 T9821 dobj cre,inherited
R2887 T9824 T9823 punct -,cre
R2888 T9825 T9826 punct (,3A
R2889 T9826 T9769 parataxis 3A,detected
R2890 T9827 T9826 compound Figure,3A
R2891 T9828 T9826 punct ),3A
R2892 T9829 T9769 punct .,detected
R2893 T9831 T9832 compound Apc,transcripts
R2894 T9832 T9833 nsubjpass transcripts,analyzed
R2895 T9834 T9833 auxpass were,analyzed
R2896 T9835 T9833 advmod also,analyzed
R2897 T9836 T9833 prep by,analyzed
R2898 T9837 T9838 compound RT,PCR
R2899 T9838 T9836 pobj PCR,by
R2900 T9839 T9838 punct -,PCR
R2901 T9840 T9838 prep with,PCR
R2902 T9841 T9840 pobj primers,with
R2903 T9842 T9841 acl spanning,primers
R2904 T9843 T9842 dobj exon,spanning
R2905 T9844 T9843 nummod 14,exon
R2906 T9845 T9846 punct (,1A
R2907 T9846 T9833 parataxis 1A,analyzed
R2908 T9847 T9846 compound Figure,1A
R2909 T9848 T9846 punct ),1A
R2910 T9849 T9833 advcl using,analyzed
R2911 T9850 T9851 amod total,RNA
R2912 T9851 T9849 dobj RNA,using
R2913 T9852 T9851 acl isolated,RNA
R2914 T9853 T9852 prep from,isolated
R2915 T9854 T9855 det the,samples
R2916 T9855 T9853 pobj samples,from
R2917 T9856 T9855 amod corresponding,samples
R2918 T9857 T9855 compound tissue,samples
R2919 T9858 T9833 punct .,analyzed
R2920 T9860 T9861 nsubj We,detected
R2921 T9862 T9863 det the,product
R2922 T9863 T9861 dobj product,detected
R2923 T9864 T9863 amod expected,product
R2924 T9865 T9866 compound RT,PCR
R2925 T9866 T9863 compound PCR,product
R2926 T9867 T9866 punct -,PCR
R2927 T9868 T9869 punct (,bp
R2928 T9869 T9863 parataxis bp,product
R2929 T9870 T9869 nummod 313,bp
R2930 T9871 T9869 punct ),bp
R2931 T9872 T9863 prep from,product
R2932 T9873 T9874 det the,allele
R2933 T9874 T9872 pobj allele,from
R2934 T9875 T9876 amod truncated,Apc
R2935 T9876 T9874 nmod Apc,allele
R2936 T9877 T9876 punct (,Apc
R2937 T9878 T9876 appos ApcΔ580,Apc
R2938 T9879 T9874 punct ),allele
R2939 T9880 T9881 advmod only,in
R2940 T9881 T9861 prep in,detected
R2941 T9882 T9883 det the,tissues
R2942 T9883 T9881 pobj tissues,in
R2943 T9884 T9885 advmod where,known
R2944 T9885 T9883 advcl known,tissues
R2945 T9886 T9887 compound Cre,recombinase
R2946 T9887 T9885 nsubjpass recombinase,known
R2947 T9888 T9885 auxpass is,known
R2948 T9889 T9890 aux to,expressed
R2949 T9890 T9885 xcomp expressed,known
R2950 T9891 T9890 auxpass be,expressed
R2951 T9892 T9890 prep in,expressed
R2952 T9893 T9894 det the,mice
R2953 T9894 T9892 pobj mice,in
R2954 T9895 T9896 compound K14,cre
R2955 T9896 T9898 npadvmod cre,positive
R2956 T9897 T9896 punct -,cre
R2957 T9898 T9894 amod positive,mice
R2958 T9899 T9898 punct –,positive
R2959 T9900 T9861 punct .,detected
R2960 T9902 T9903 advmod However,detected
R2961 T9904 T9903 punct ", ",detected
R2962 T9905 T9906 det this,product
R2963 T9906 T9903 nsubjpass product,detected
R2964 T9907 T9903 auxpass was,detected
R2965 T9908 T9903 neg not,detected
R2966 T9909 T9903 prep in,detected
R2967 T9910 T9911 preconj either,samples
R2968 T9911 T9909 pobj samples,in
R2969 T9912 T9911 det the,samples
R2970 T9913 T9914 compound K14,cre
R2971 T9914 T9916 npadvmod cre,negative
R2972 T9915 T9914 punct -,cre
R2973 T9916 T9911 amod negative,samples
R2974 T9917 T9916 punct –,negative
R2975 T9918 T9919 compound mouse,tissues
R2976 T9919 T9911 compound tissues,samples
R2977 T9920 T9911 cc or,samples
R2978 T9921 T9922 det the,liver
R2979 T9922 T9911 conj liver,samples
R2980 T9923 T9922 prep of,liver
R2981 T9924 T9925 compound K14,cre
R2982 T9925 T9927 npadvmod cre,positive
R2983 T9926 T9925 punct -,cre
R2984 T9927 T9929 amod positive,mice
R2985 T9928 T9927 punct –,positive
R2986 T9929 T9923 pobj mice,of
R2987 T9930 T9903 punct ", ",detected
R2988 T9931 T9903 cc and,detected
R2989 T9932 T9933 advmod only,product
R2990 T9933 T9935 nsubjpass product,detected
R2991 T9934 T9933 det the,product
R2992 T9935 T9903 conj detected,detected
R2993 T9936 T9933 prep from,product
R2994 T9937 T9938 det the,allele
R2995 T9938 T9936 pobj allele,from
R2996 T9939 T9940 amod wild,type
R2997 T9940 T9938 compound type,allele
R2998 T9941 T9940 punct -,type
R2999 T9942 T9943 punct (,bp
R3000 T9943 T9933 parataxis bp,product
R3001 T9944 T9943 nummod 528,bp
R3002 T9945 T9943 punct ),bp
R3003 T9946 T9935 auxpass was,detected
R3004 T9947 T9935 prep from,detected
R3005 T9948 T9949 det these,samples
R3006 T9949 T9947 pobj samples,from
R3007 T9950 T9949 compound RNA,samples
R3008 T9951 T9935 punct ", ",detected
R3009 T9952 T9953 advmod further,confirming
R3010 T9953 T9935 advcl confirming,detected
R3011 T9954 T9955 mark that,taken
R3012 T9955 T9953 ccomp taken,confirming
R3013 T9956 T9957 npadvmod Cre,mediated
R3014 T9957 T9959 amod mediated,recombination
R3015 T9958 T9957 punct -,mediated
R3016 T9959 T9955 nsubj recombination,taken
R3017 T9960 T9955 aux has,taken
R3018 T9961 T9955 dobj place,taken
R3019 T9962 T9955 prep in,taken
R3020 T9963 T9964 det the,manner
R3021 T9964 T9962 pobj manner,in
R3022 T9965 T9966 npadvmod tissue,specific
R3023 T9966 T9964 amod specific,manner
R3024 T9967 T9965 punct -,tissue
R3025 T9968 T9965 cc and,tissue
R3026 T9969 T9965 conj genotype,tissue
R3027 T9970 T9966 punct -,specific
R3028 T9971 T9972 punct (,3B
R3029 T9972 T9935 parataxis 3B,detected
R3030 T9973 T9972 compound Figure,3B
R3031 T9974 T9972 punct ),3B
R3032 T9975 T9903 punct .,detected
R3047 T12568 T12569 amod K14,cre
R3048 T12569 T12571 amod cre,Driven
R3049 T12570 T12569 punct -,cre
R3050 T12571 T12573 amod Driven,Follicles
R3051 T12572 T12571 punct –,Driven
R3052 T12574 T12575 compound Apc,Loss
R3053 T12575 T12576 npadvmod Loss,Induced
R3054 T12576 T12573 amod Induced,Follicles
R3055 T12577 T12573 compound Aberrant,Follicles
R3056 T12578 T12573 compound Hair,Follicles
R3057 T12579 T12573 prep throughout,Follicles
R3058 T12580 T12581 det the,Epidermis
R3059 T12581 T12579 pobj Epidermis,throughout
R3060 T12583 T12584 aux To,understand
R3061 T12584 T12585 advcl understand,conducted
R3062 T12586 T12587 det the,basis
R3063 T12587 T12584 dobj basis,understand
R3064 T12588 T12587 prep for,basis
R3065 T12589 T12590 amod delayed,development
R3066 T12590 T12588 pobj development,for
R3067 T12591 T12589 cc and,delayed
R3068 T12592 T12589 conj abnormal,delayed
R3069 T12593 T12590 compound hair,development
R3070 T12594 T12590 prep in,development
R3071 T12595 T12596 det the,mutants
R3072 T12596 T12594 pobj mutants,in
R3073 T12597 T12596 compound KA,mutants
R3074 T12598 T12585 punct ", ",conducted
R3075 T12599 T12585 nsubj we,conducted
R3076 T12600 T12601 det a,examination
R3077 T12601 T12585 dobj examination,conducted
R3078 T12602 T12601 amod histological,examination
R3079 T12603 T12602 cc and,histological
R3080 T12604 T12602 conj immunohistochemical,histological
R3081 T12605 T12606 punct (,Figure
R3082 T12606 T12585 parataxis Figure,conducted
R3083 T12607 T12606 nummod 4,Figure
R3084 T12608 T12606 punct ),Figure
R3085 T12609 T12585 punct .,conducted
R3086 T12611 T12612 det The,follicle
R3087 T12612 T12614 nsubj follicle,is
R3088 T12613 T12612 compound hair,follicle
R3089 T12615 T12616 det an,appendage
R3090 T12616 T12614 attr appendage,is
R3091 T12617 T12616 amod epidermal,appendage
R3092 T12618 T12619 dep that,consists
R3093 T12619 T12616 relcl consists,appendage
R3094 T12620 T12619 prep of,consists
R3095 T12621 T12622 det an,portion
R3096 T12622 T12620 pobj portion,of
R3097 T12623 T12622 amod upper,portion
R3098 T12624 T12622 amod permanent,portion
R3099 T12625 T12622 punct ", ",portion
R3100 T12626 T12622 cc and,portion
R3101 T12627 T12628 det a,portion
R3102 T12628 T12622 conj portion,portion
R3103 T12629 T12628 amod lower,portion
R3104 T12630 T12628 compound cycling,portion
R3105 T12631 T12632 dep that,produces
R3106 T12632 T12628 relcl produces,portion
R3107 T12633 T12634 det the,hair
R3108 T12634 T12632 dobj hair,produces
R3109 T12635 T12636 punct [,23
R3110 T12636 T12614 parataxis 23,is
R3111 T12637 T12636 nummod 22,23
R3112 T12638 T12636 punct ",",23
R3113 T12639 T12636 punct ],23
R3114 T12640 T12614 punct .,is
R3115 T12642 T12643 det The,sheath
R3116 T12643 T12646 nsubj sheath,is
R3117 T12644 T12643 amod outer,sheath
R3118 T12645 T12643 compound root,sheath
R3119 T12647 T12643 punct (,sheath
R3120 T12648 T12643 appos ORS,sheath
R3121 T12649 T12646 punct ),is
R3122 T12650 T12646 acomp contiguous,is
R3123 T12651 T12650 prep with,contiguous
R3124 T12652 T12650 cc and,contiguous
R3125 T12653 T12654 advmod biochemically,similar
R3126 T12654 T12650 conj similar,contiguous
R3127 T12655 T12654 prep to,similar
R3128 T12656 T12657 det the,layer
R3129 T12657 T12654 npadvmod layer,similar
R3130 T12658 T12657 amod basal,layer
R3131 T12659 T12657 prep of,layer
R3132 T12660 T12661 det the,epidermis
R3133 T12661 T12659 pobj epidermis,of
R3134 T12662 T12646 punct .,is
R3135 T12664 T12665 det The,layers
R3136 T12665 T12667 nsubj layers,include
R3137 T12666 T12665 amod inner,layers
R3138 T12668 T12665 prep of,layers
R3139 T12669 T12670 det the,follicle
R3140 T12670 T12668 pobj follicle,of
R3141 T12671 T12670 compound hair,follicle
R3142 T12672 T12673 nummod three,layers
R3143 T12673 T12667 dobj layers,include
R3144 T12674 T12673 amod concentric,layers
R3145 T12675 T12673 prep of,layers
R3146 T12676 T12677 amod inner,sheath
R3147 T12677 T12675 pobj sheath,of
R3148 T12678 T12677 compound root,sheath
R3149 T12679 T12673 cc and,layers
R3150 T12680 T12681 nummod three,layers
R3151 T12681 T12673 conj layers,layers
R3152 T12682 T12681 amod concentric,layers
R3153 T12683 T12681 prep of,layers
R3154 T12684 T12685 npadvmod hair,producing
R3155 T12685 T12687 amod producing,cells
R3156 T12686 T12685 punct -,producing
R3157 T12687 T12683 pobj cells,of
R3158 T12688 T12667 punct .,include
R3159 T12690 T12691 prep At,is
R3160 T12692 T12693 det the,base
R3161 T12693 T12690 pobj base,At
R3162 T12694 T12693 prep of,base
R3163 T12695 T12696 det the,follicle
R3164 T12696 T12694 pobj follicle,of
R3165 T12697 T12696 compound hair,follicle
R3166 T12698 T12699 det the,bulb
R3167 T12699 T12691 nsubj bulb,is
R3168 T12700 T12699 amod germinative,bulb
R3169 T12701 T12702 compound hair,follicle
R3170 T12702 T12699 compound follicle,bulb
R3171 T12703 T12699 punct ", ",bulb
R3172 T12704 T12705 dep which,contains
R3173 T12705 T12699 relcl contains,bulb
R3174 T12706 T12707 advmod rapidly,proliferating
R3175 T12707 T12708 amod proliferating,cells
R3176 T12708 T12705 dobj cells,contains
R3177 T12709 T12708 punct “,cells
R3178 T12710 T12708 nmod matrix,cells
R3179 T12711 T12708 punct ”,cells
R3180 T12712 T12713 dep that,differentiate
R3181 T12713 T12708 relcl differentiate,cells
R3182 T12714 T12715 aux to,populate
R3183 T12715 T12713 advcl populate,differentiate
R3184 T12716 T12715 dobj all,populate
R3185 T12717 T12716 prep of,all
R3186 T12718 T12719 det the,layers
R3187 T12719 T12717 pobj layers,of
R3188 T12720 T12719 prep of,layers
R3189 T12721 T12722 det the,sheath
R3190 T12722 T12720 pobj sheath,of
R3191 T12723 T12722 amod inner,sheath
R3192 T12724 T12722 compound root,sheath
R3193 T12725 T12716 cc and,all
R3194 T12726 T12727 det the,shaft
R3195 T12727 T12716 conj shaft,all
R3196 T12728 T12727 compound hair,shaft
R3197 T12729 T12727 appos itself,shaft
R3198 T12730 T12731 punct [,22
R3199 T12731 T12691 parataxis 22,is
R3200 T12732 T12731 punct ],22
R3201 T12733 T12691 punct .,is
R3202 T12735 T12736 prep During,grew
R3203 T12737 T12738 det the,phase
R3204 T12738 T12735 pobj phase,During
R3205 T12739 T12738 compound anagen,phase
R3206 T12740 T12738 prep of,phase
R3207 T12741 T12742 det the,cycle
R3208 T12742 T12740 pobj cycle,of
R3209 T12743 T12742 compound hair,cycle
R3210 T12744 T12745 punct (,until
R3211 T12745 T12738 parataxis until,phase
R3212 T12746 T12745 pobj P15,until
R3213 T12747 T12745 punct ),until
R3214 T12748 T12736 punct ", ",grew
R3215 T12749 T12750 compound hair,follicles
R3216 T12750 T12736 nsubj follicles,grew
R3217 T12751 T12750 prep of,follicles
R3218 T12752 T12753 advmod phenotypically,mice
R3219 T12753 T12751 pobj mice,of
R3220 T12754 T12753 amod normal,mice
R3221 T12755 T12736 advmod deeply,grew
R3222 T12756 T12736 prep into,grew
R3223 T12757 T12758 det the,fat
R3224 T12758 T12756 pobj fat,into
R3225 T12759 T12758 amod subcutaneous,fat
R3226 T12760 T12736 cc and,grew
R3227 T12761 T12762 auxpass were,spaced
R3228 T12762 T12736 conj spaced,grew
R3229 T12763 T12762 advmod uniformly,spaced
R3230 T12764 T12762 cc and,spaced
R3231 T12765 T12762 conj aligned,spaced
R3232 T12766 T12765 prep in,aligned
R3233 T12767 T12768 amod parallel,arrays
R3234 T12768 T12766 pobj arrays,in
R3235 T12769 T12765 prep at,aligned
R3236 T12770 T12771 det a,angle
R3237 T12771 T12769 pobj angle,at
R3238 T12772 T12771 amod specific,angle
R3239 T12773 T12771 amod relative,angle
R3240 T12774 T12773 prep to,relative
R3241 T12775 T12776 det the,surface
R3242 T12776 T12774 pobj surface,to
R3243 T12777 T12776 compound skin,surface
R3244 T12778 T12779 punct (,4A
R3245 T12779 T12765 parataxis 4A,aligned
R3246 T12780 T12779 compound Figure,4A
R3247 T12781 T12779 punct ),4A
R3248 T12782 T12736 punct .,grew
R3249 T12784 T12785 prep In,spaced
R3250 T12786 T12784 pobj contrast,In
R3251 T12787 T12785 punct ", ",spaced
R3252 T12788 T12789 nmod KA,follicles
R3253 T12789 T12785 nsubjpass follicles,spaced
R3254 T12790 T12789 amod mutant,follicles
R3255 T12791 T12785 auxpass were,spaced
R3256 T12792 T12785 advmod irregularly,spaced
R3257 T12793 T12785 cc and,spaced
R3258 T12794 T12795 advmod often,seen
R3259 T12795 T12785 conj seen,spaced
R3260 T12796 T12795 prep as,seen
R3261 T12797 T12798 amod disoriented,invaginations
R3262 T12798 T12796 pobj invaginations,as
R3263 T12799 T12797 cc and,disoriented
R3264 T12800 T12797 conj clamped,disoriented
R3265 T12801 T12798 prep at,invaginations
R3266 T12802 T12801 pobj P3,at
R3267 T12803 T12804 dep that,became
R3268 T12804 T12798 relcl became,invaginations
R3269 T12805 T12806 advmod even,more
R3270 T12806 T12807 advmod more,remarkable
R3271 T12807 T12804 acomp remarkable,became
R3272 T12808 T12804 prep at,became
R3273 T12809 T12808 pobj P12,at
R3274 T12810 T12811 advmod when,covered
R3275 T12811 T12809 advcl covered,P12
R3276 T12812 T12813 det the,mice
R3277 T12813 T12811 nsubjpass mice,covered
R3278 T12814 T12813 amod mutant,mice
R3279 T12815 T12811 auxpass were,covered
R3280 T12816 T12811 agent by,covered
R3281 T12817 T12818 compound fur,coat
R3282 T12818 T12816 pobj coat,by
R3283 T12819 T12820 punct (,4F
R3284 T12820 T12795 parataxis 4F,seen
R3285 T12821 T12820 compound Figure,4F
R3286 T12822 T12820 punct ),4F
R3287 T12823 T12785 punct .,spaced
R3288 T12825 T12826 nsubj Bulbs,were
R3289 T12827 T12826 advmod often,were
R3290 T12828 T12826 acomp bent,were
R3291 T12829 T12826 prep in,were
R3292 T12830 T12829 pobj addition,in
R3293 T12831 T12830 prep to,addition
R3294 T12832 T12831 pcomp being,to
R3295 T12833 T12834 advmod irregularly,angled
R3296 T12834 T12832 acomp angled,being
R3297 T12835 T12834 prep to,angled
R3298 T12836 T12837 compound one,another
R3299 T12837 T12835 pobj another,to
R3300 T12838 T12826 cc and,were
R3301 T12839 T12840 poss their,sizes
R3302 T12840 T12841 nsubj sizes,were
R3303 T12841 T12826 conj were,were
R3304 T12842 T12840 cc and,sizes
R3305 T12843 T12840 conj locations,sizes
R3306 T12844 T12841 advmod often,were
R3307 T12845 T12841 acomp variable,were
R3308 T12846 T12841 punct .,were
R3309 T12848 T12849 nsubjpass Clusters,observed
R3310 T12850 T12848 prep of,Clusters
R3311 T12851 T12852 amod multiple,invaginations
R3312 T12852 T12850 pobj invaginations,of
R3313 T12853 T12852 cc or,invaginations
R3314 T12854 T12855 amod dysplastic,structures
R3315 T12855 T12852 conj structures,invaginations
R3316 T12856 T12855 amod follicular,structures
R3317 T12857 T12849 auxpass were,observed
R3318 T12858 T12849 advmod frequently,observed
R3319 T12859 T12849 prep throughout,observed
R3320 T12860 T12861 det the,epidermis
R3321 T12861 T12859 pobj epidermis,throughout
R3322 T12862 T12849 punct ", ",observed
R3323 T12863 T12864 mark whereas,showed
R3324 T12864 T12849 advcl showed,observed
R3325 T12865 T12866 amod other,regions
R3326 T12866 T12864 nsubj regions,showed
R3327 T12867 T12864 dobj gaps,showed
R3328 T12868 T12867 prep with,gaps
R3329 T12869 T12870 det no,follicles
R3330 T12870 T12868 pobj follicles,with
R3331 T12871 T12849 punct .,observed
R3332 T12873 T12874 amod Serial,sectioning
R3333 T12874 T12875 nsubj sectioning,indicated
R3334 T12876 T12877 mark that,were
R3335 T12877 T12875 ccomp were,indicated
R3336 T12878 T12877 nsubj some,were
R3337 T12879 T12878 prep of,some
R3338 T12880 T12881 det the,follicles
R3339 T12881 T12879 pobj follicles,of
R3340 T12882 T12881 compound hair,follicles
R3341 T12883 T12881 prep in,follicles
R3342 T12884 T12885 det the,skin
R3343 T12885 T12883 pobj skin,in
R3344 T12886 T12885 nmod P12,skin
R3345 T12887 T12885 amod mutant,skin
R3346 T12888 T12877 neg not,were
R3347 T12889 T12890 advmod properly,formed
R3348 T12890 T12877 acomp formed,were
R3349 T12891 T12877 cc or,were
R3350 T12892 T12877 conj shorter,were
R3351 T12893 T12892 prep than,shorter
R3352 T12894 T12893 amod normal,than
R3353 T12895 T12875 punct .,indicated
R3354 T12897 T12898 advcl Taken,account
R3355 T12899 T12897 advmod together,Taken
R3356 T12900 T12898 punct ", ",account
R3357 T12901 T12902 det these,features
R3358 T12902 T12898 nsubj features,account
R3359 T12903 T12898 aux could,account
R3360 T12904 T12898 prep for,account
R3361 T12905 T12906 det the,delayed
R3362 T12906 T12904 pobj delayed,for
R3363 T12907 T12906 advmod apparently,delayed
R3364 T12908 T12906 punct ", ",delayed
R3365 T12909 T12906 acl followed,delayed
R3366 T12910 T12909 agent by,followed
R3367 T12911 T12910 pobj outgrowth,by
R3368 T12912 T12906 punct ", ",delayed
R3369 T12913 T12906 prep of,delayed
R3370 T12914 T12915 det the,coat
R3371 T12915 T12913 pobj coat,of
R3372 T12916 T12915 amod short,coat
R3373 T12917 T12916 cc and,short
R3374 T12918 T12919 amod shaggy,looking
R3375 T12919 T12916 conj looking,short
R3376 T12920 T12919 punct -,looking
R3377 T12921 T12915 compound fur,coat
R3378 T12922 T12915 prep of,coat
R3379 T12923 T12924 det these,mice
R3380 T12924 T12922 pobj mice,of
R3381 T12925 T12924 amod mutant,mice
R3382 T12926 T12898 punct .,account
R3383 T12928 T12929 nsubj Apc,is
R3384 T12930 T12931 det a,regulator
R3385 T12931 T12929 attr regulator,is
R3386 T12932 T12931 prep of,regulator
R3387 T12933 T12934 compound β,catenin
R3388 T12934 T12932 pobj catenin,of
R3389 T12935 T12934 punct -,catenin
R3390 T12936 T12937 dep that,is
R3391 T12937 T12931 relcl is,regulator
R3392 T12938 T12937 acomp important,is
R3393 T12939 T12938 prep for,important
R3394 T12940 T12941 compound Wnt,signaling
R3395 T12941 T12939 pobj signaling,for
R3396 T12942 T12929 punct .,is
R3397 T12944 T12945 nsubj We,examined
R3398 T12946 T12947 det the,patterns
R3399 T12947 T12945 dobj patterns,examined
R3400 T12948 T12947 prep of,patterns
R3401 T12949 T12948 pobj expression,of
R3402 T12950 T12949 prep of,expression
R3403 T12951 T12952 compound β,catenin
R3404 T12952 T12950 pobj catenin,of
R3405 T12953 T12952 punct -,catenin
R3406 T12954 T12945 prep in,examined
R3407 T12955 T12956 det the,tissues
R3408 T12956 T12954 pobj tissues,in
R3409 T12957 T12956 amod affected,tissues
R3410 T12958 T12945 punct .,examined
R3411 T12960 T12961 prep In,found
R3412 T12962 T12963 det the,skin
R3413 T12963 T12960 pobj skin,In
R3414 T12964 T12963 amod normal,skin
R3415 T12965 T12961 punct ", ",found
R3416 T12966 T12967 compound β,catenin
R3417 T12967 T12961 nsubjpass catenin,found
R3418 T12968 T12967 punct -,catenin
R3419 T12969 T12967 punct ", ",catenin
R3420 T13040 T13038 prep of,patterns
R3421 T12970 T12971 det a,member
R3422 T13041 T13040 pobj expression,of
R3423 T12971 T12967 appos member,catenin
R3424 T13042 T13041 prep of,expression
R3425 T13043 T13042 pobj K14,of
R3426 T12972 T12971 prep of,member
R3427 T13044 T13043 punct ", ",K14
R3428 T13045 T13043 conj K1,K14
R3429 T13046 T13045 punct ", ",K1
R3430 T12973 T12974 det the,complex
R3431 T13047 T13045 conj involucrin,K1
R3432 T13048 T13047 punct ", ",involucrin
R3433 T12974 T12972 pobj complex,of
R3434 T13049 T13047 cc and,involucrin
R3435 T13050 T13047 conj loricrin,involucrin
R3436 T13051 T13041 punct ", ",expression
R3437 T12975 T12976 compound adherens,junction
R3438 T13052 T13041 prep in,expression
R3439 T13053 T13052 pobj skin,in
R3440 T13054 T13053 prep from,skin
R3441 T12976 T12974 compound junction,complex
R3442 T13055 T13056 amod mutant,littermate
R3443 T13056 T13059 nmod littermate,mice
R3444 T13057 T13055 cc and,mutant
R3445 T13058 T13055 conj normal,mutant
R3446 T13059 T13054 pobj mice,from
R3447 T13060 T13041 prep at,expression
R3448 T13061 T13060 pobj P3,at
R3449 T12977 T12961 punct ", ",found
R3450 T13062 T13063 punct –,P17
R3451 T13063 T13061 prep P17,P3
R3452 T13064 T13039 punct ", ",showed
R3453 T12978 T12961 auxpass was,found
R3454 T13065 T13066 det no,differences
R3455 T13066 T13039 dobj differences,showed
R3456 T13067 T13066 amod significant,differences
R3457 T12979 T12961 prep in,found
R3458 T13068 T13066 prep in,differences
R3459 T13069 T13070 det the,differentiation
R3460 T12980 T12981 det the,ORS
R3461 T13070 T13068 pobj differentiation,in
R3462 T13071 T13070 amod terminal,differentiation
R3463 T13072 T13073 punct (,4A
R3464 T12981 T12979 pobj ORS,in
R3465 T13073 T13066 parataxis 4A,differences
R3466 T13074 T13073 compound Figure,4A
R3467 T13075 T13076 punct –,4D
R3468 T13076 T13073 prep 4D,4A
R3469 T12982 T12981 prep of,ORS
R3470 T13077 T13073 punct ", ",4A
R3471 T13078 T13073 appos 4F,4A
R3472 T12983 T12984 compound hair,follicles
R3473 T13079 T13080 punct –,4I
R3474 T13080 T13078 prep 4I,4F
R3475 T12984 T12982 pobj follicles,of
R3476 T12985 T12981 cc and,ORS
R3477 T13081 T13073 punct ),4A
R3478 T13082 T13039 punct .,showed
R3479 T12986 T12987 amod basal,layer
R3480 T13084 T13085 advmod Similarly,change
R3481 T12987 T12981 conj layer,ORS
R3482 T13086 T13085 punct ", ",change
R3483 T13087 T13088 det the,pattern
R3484 T12988 T12987 prep of,layer
R3485 T13088 T13085 nsubj pattern,change
R3486 T13089 T13088 prep of,pattern
R3487 T13090 T13089 pobj expression,of
R3488 T12989 T12988 pobj epidermis,of
R3489 T13091 T13088 prep of,pattern
R3490 T13092 T13091 pobj K6,of
R3491 T12990 T12981 punct ", ",ORS
R3492 T13093 T13092 punct ", ",K6
R3493 T13094 T13095 dep which,expressed
R3494 T12991 T12992 advmod where,observed
R3495 T13095 T13092 relcl expressed,K6
R3496 T13096 T13095 auxpass is,expressed
R3497 T13097 T13095 advmod normally,expressed
R3498 T13098 T13095 advmod only,expressed
R3499 T13099 T13095 prep in,expressed
R3500 T13100 T13101 det the,layer
R3501 T13101 T13099 pobj layer,in
R3502 T12992 T12981 advcl observed,ORS
R3503 T13102 T13101 amod suprabasal,layer
R3504 T13103 T13102 cc or,suprabasal
R3505 T13104 T13102 conj inner,suprabasal
R3506 T12993 T12994 compound K14,expression
R3507 T13105 T13101 prep of,layer
R3508 T13106 T13107 det the,ORS
R3509 T13107 T13105 pobj ORS,of
R3510 T13108 T13107 prep of,ORS
R3511 T12994 T12992 nsubjpass expression,observed
R3512 T13109 T13110 det the,follicle
R3513 T13110 T13108 pobj follicle,of
R3514 T12995 T12992 auxpass is,observed
R3515 T13111 T13110 compound hair,follicle
R3516 T13112 T13099 cc but,in
R3517 T13113 T13112 neg not,but
R3518 T12996 T12992 advmod also,observed
R3519 T13114 T13099 conj in,in
R3520 T13115 T13116 det the,epidermis
R3521 T13116 T13114 pobj epidermis,in
R3522 T13117 T13118 punct (,4E
R3523 T12997 T12998 punct (,4C
R3524 T13118 T13088 parataxis 4E,pattern
R3525 T13119 T13118 compound Figure,4E
R3526 T13120 T13118 punct ),4E
R3527 T12998 T12961 parataxis 4C,found
R3528 T13121 T13085 punct ", ",change
R3529 T13122 T13085 aux did,change
R3530 T13123 T13085 neg not,change
R3531 T12999 T12998 compound Figure,4C
R3532 T13124 T13085 punct .,change
R3533 T13000 T12998 cc and,4C
R3534 T13126 T13127 prep Due,highlighted
R3535 T13128 T13126 pcomp to,Due
R3536 T13001 T12998 conj 4D,4C
R3537 T13129 T13130 det the,structure
R3538 T13130 T13126 pobj structure,Due
R3539 T13131 T13130 amod abnormal,structure
R3540 T13002 T12998 punct ),4C
R3541 T13132 T13131 cc and,abnormal
R3542 T13133 T13131 conj disorganized,abnormal
R3543 T13003 T12961 punct ", ",found
R3544 T13134 T13130 prep of,structure
R3545 T13135 T13136 compound hair,follicles
R3546 T13136 T13134 pobj follicles,of
R3547 T13004 T13005 mark whereas,observed
R3548 T13137 T13136 appos themselves,follicles
R3549 T13138 T13127 punct ", ",highlighted
R3550 T13139 T13140 compound K6,localization
R3551 T13140 T13127 nsubj localization,highlighted
R3552 T13141 T13142 det the,abnormality
R3553 T13005 T12961 advcl observed,found
R3554 T13142 T13127 dobj abnormality,highlighted
R3555 T13143 T13142 amod histological,abnormality
R3556 T13144 T13145 punct (,4J
R3557 T13006 T13007 det the,expression
R3558 T13007 T13005 nsubjpass expression,observed
R3559 T13008 T13007 prep of,expression
R3560 T13145 T13127 parataxis 4J,highlighted
R3561 T13009 T13008 pobj K1,of
R3562 T13146 T13145 compound Figure,4J
R3563 T13147 T13145 punct ),4J
R3564 T13010 T13009 punct ", ",K1
R3565 T13148 T13127 punct .,highlighted
R3566 T13150 T13151 advmod Yet,seen
R3567 T13011 T13009 conj involucrin,K1
R3568 T13152 T13151 prep as,seen
R3569 T13012 T13011 punct ", ",involucrin
R3570 T13153 T13152 prep in,as
R3571 T13154 T13155 det the,skin
R3572 T13013 T13011 cc and,involucrin
R3573 T13155 T13153 pobj skin,in
R3574 T13156 T13155 amod normal,skin
R3575 T13157 T13151 punct ", ",seen
R3576 T13158 T13151 nsubjpass K6,seen
R3577 T13014 T13011 conj loricrin,involucrin
R3578 T13159 T13151 auxpass was,seen
R3579 T13160 T13151 advmod principally,seen
R3580 T13161 T13162 advmod only,in
R3581 T13015 T13009 punct (,K1
R3582 T13162 T13151 prep in,seen
R3583 T13163 T13164 det the,layer
R3584 T13164 T13162 pobj layer,in
R3585 T13016 T13009 appos markers,K1
R3586 T13165 T13164 amod suprabasal,layer
R3587 T13166 T13164 prep of,layer
R3588 T13167 T13168 det the,ORS
R3589 T13017 T13016 prep for,markers
R3590 T13018 T13019 amod spinous,layers
R3591 T13168 T13166 pobj ORS,of
R3592 T13169 T13170 dep that,colocalize
R3593 T13019 T13017 pobj layers,for
R3594 T13170 T13168 relcl colocalize,ORS
R3595 T13171 T13170 aux did,colocalize
R3596 T13172 T13170 neg not,colocalize
R3597 T13020 T13018 cc and,spinous
R3598 T13173 T13170 prep with,colocalize
R3599 T13174 T13175 det the,markers
R3600 T13175 T13173 pobj markers,with
R3601 T13176 T13175 amod basal,markers
R3602 T13177 T13175 punct ", ",markers
R3603 T13178 T13175 appos K14,markers
R3604 T13021 T13018 conj granular,spinous
R3605 T13179 T13178 cc or,K14
R3606 T13180 T13178 conj K5,K14
R3607 T13181 T13182 punct (,4I
R3608 T13182 T13151 parataxis 4I,seen
R3609 T13022 T13019 prep of,layers
R3610 T13183 T13182 compound Figure,4I
R3611 T13184 T13182 cc and,4I
R3612 T13023 T13022 pobj epidermis,of
R3613 T13185 T13182 conj 4J,4I
R3614 T13186 T13182 punct ),4I
R3615 T13187 T13151 punct .,seen
R3616 T13024 T13005 punct ),observed
R3617 T13189 T13190 prep In,detected
R3618 T13025 T13005 auxpass was,observed
R3619 T13191 T13192 amod normal,skin
R3620 T13192 T13189 pobj skin,In
R3621 T13193 T13190 punct ", ",detected
R3622 T13026 T13005 advmod only,observed
R3623 T13194 T13195 amod proliferating,cells
R3624 T13195 T13190 nsubjpass cells,detected
R3625 T13027 T13005 prep in,observed
R3626 T13196 T13190 auxpass were,detected
R3627 T13197 T13190 prep in,detected
R3628 T13198 T13197 preconj either,in
R3629 T13028 T13029 det the,epidermis
R3630 T13199 T13200 det the,layer
R3631 T13200 T13197 conj layer,in
R3632 T13201 T13200 amod basal,layer
R3633 T13202 T13200 prep of,layer
R3634 T13029 T13027 pobj epidermis,in
R3635 T13203 T13202 pobj epidermis,of
R3636 T13204 T13197 cc or,in
R3637 T13205 T13197 conj in,in
R3638 T13030 T13029 amod nonbasal,epidermis
R3639 T13206 T13207 amod germinative,bulbs
R3640 T13207 T13205 pobj bulbs,in
R3641 T13031 T13032 punct (,data
R3642 T13208 T13209 compound hair,follicle
R3643 T13209 T13207 compound follicle,bulbs
R3644 T13210 T13207 prep at,bulbs
R3645 T13032 T13005 parataxis data,observed
R3646 T13211 T13212 det the,base
R3647 T13212 T13210 pobj base,at
R3648 T13213 T13214 punct (,4B
R3649 T13214 T13190 parataxis 4B,detected
R3650 T13033 T13032 amod unpublished,data
R3651 T13215 T13214 compound Figure,4B
R3652 T13216 T13214 punct ),4B
R3653 T13217 T13190 punct .,detected
R3654 T13219 T13220 prep In,observed
R3655 T13034 T13032 punct ),data
R3656 T13221 T13222 det the,skin
R3657 T13222 T13219 pobj skin,In
R3658 T13223 T13222 amod mutant,skin
R3659 T13035 T12961 punct .,found
R3660 T13224 T13220 punct ", ",observed
R3661 T13225 T13226 preconj either,incorporation
R3662 T13226 T13220 nsubjpass incorporation,observed
R3663 T13227 T13226 compound BrdU,incorporation
R3664 T13037 T13038 det The,patterns
R3665 T13228 T13226 cc or,incorporation
R3666 T13229 T13230 compound Ki67,expression
R3667 T13230 T13226 conj expression,incorporation
R3668 T13231 T13220 auxpass was,observed
R3669 T13038 T13039 nsubj patterns,showed
R3670 T13232 T13233 preconj not,in
R3671 T13233 T13220 prep in,observed
R3672 T13234 T13232 advmod only,not
R3673 T13235 T13233 pobj cells,in
R3674 T13251 T13247 pobj structures,in
R3675 T13236 T13235 prep in,cells
R3676 T13237 T13236 pobj bulbs,in
R3677 T13238 T13237 prep at,bulbs
R3678 T13239 T13240 det the,base
R3679 T13252 T13253 dep that,budding
R3680 T13240 T13238 pobj base,at
R3681 T13241 T13240 prep of,base
R3682 T13242 T13243 det the,follicle
R3683 T13243 T13241 pobj follicle,of
R3684 T13253 T13251 relcl budding,structures
R3685 T13244 T13243 compound hair,follicle
R3686 T13245 T13233 cc but,in
R3687 T13246 T13245 advmod also,but
R3688 T13254 T13253 aux were,budding
R3689 T13247 T13233 conj in,in
R3690 T13248 T13249 npadvmod bulb,like
R3691 T13249 T13251 amod like,structures
R3692 T13255 T13253 prt out,budding
R3693 T13250 T13249 punct -,like
R3694 T13256 T13253 prep from,budding
R3695 T13257 T13258 det the,ORS
R3696 T13258 T13256 pobj ORS,from
R3697 T13259 T13258 prep of,ORS
R3698 T13260 T13261 det the,follicles
R3699 T13261 T13259 pobj follicles,of
R3700 T13357 T13356 prep to,addition
R3701 T13358 T13359 amod diffuse,localization
R3702 T13262 T13261 amod existing,follicles
R3703 T13359 T13357 pobj localization,to
R3704 T13360 T13361 npadvmod membrane,bound
R3705 T13263 T13261 compound hair,follicles
R3706 T13361 T13359 amod bound,localization
R3707 T13362 T13361 punct -,bound
R3708 T13363 T13348 prep as,observed
R3709 T13364 T13363 prep in,as
R3710 T13365 T13366 det the,skin
R3711 T13366 T13364 pobj skin,in
R3712 T13264 T13265 punct (,4G
R3713 T13367 T13366 amod normal,skin
R3714 T13368 T13348 punct ", ",observed
R3715 T13265 T13220 parataxis 4G,observed
R3716 T13369 T13348 nsubjpass cells,observed
R3717 T13370 T13369 prep with,cells
R3718 T13371 T13372 amod strong,localization
R3719 T13266 T13265 compound Figure,4G
R3720 T13372 T13370 pobj localization,with
R3721 T13373 T13374 amod cytosolic,β
R3722 T13374 T13372 nmod β,localization
R3723 T13267 T13265 cc and,4G
R3724 T13375 T13374 punct -,β
R3725 T13376 T13374 appos catenin,β
R3726 T13268 T13265 conj 4G,4G
R3727 T13377 T13348 auxpass were,observed
R3728 T13378 T13348 advmod also,observed
R3729 T13269 T13268 punct ′,4G
R3730 T13379 T13348 advmod frequently,observed
R3731 T13380 T13381 punct (,4H
R3732 T13381 T13348 parataxis 4H,observed
R3733 T13270 T13265 punct ),4G
R3734 T13382 T13381 compound Figure,4H
R3735 T13383 T13381 cc and,4H
R3736 T13271 T13220 punct .,observed
R3737 T13384 T13381 conj 4H,4H
R3738 T13385 T13384 punct ′,4H
R3739 T13386 T13381 punct ),4H
R3740 T13387 T13348 punct .,observed
R3741 T13273 T13274 det Each,tip
R3742 T13389 T13390 det These,cells
R3743 T13390 T13397 nsubjpass cells,surrounded
R3744 T13274 T13276 nsubj tip,becoming
R3745 T13391 T13390 amod elevated,cells
R3746 T13392 T13393 compound β,catenin
R3747 T13393 T13395 npadvmod catenin,expressing
R3748 T13275 T13274 amod budding,tip
R3749 T13394 T13393 punct -,catenin
R3750 T13395 T13390 amod expressing,cells
R3751 T13396 T13395 punct –,expressing
R3752 T13277 T13276 aux was,becoming
R3753 T13398 T13397 auxpass were,surrounded
R3754 T13399 T13397 advmod usually,surrounded
R3755 T13400 T13397 agent by,surrounded
R3756 T13278 T13276 prep like,becoming
R3757 T13401 T13402 amod proliferating,cells
R3758 T13402 T13400 pobj cells,by
R3759 T13403 T13397 punct ", ",surrounded
R3760 T13404 T13397 advcl forming,surrounded
R3761 T13405 T13406 npadvmod bulb,like
R3762 T13279 T13280 det a,bulb
R3763 T13406 T13408 amod like,structures
R3764 T13407 T13406 punct -,like
R3765 T13408 T13404 dobj structures,forming
R3766 T13409 T13397 punct .,surrounded
R3767 T13280 T13278 pobj bulb,like
R3768 T13411 T13412 nsubj Comparison,showed
R3769 T13281 T13282 compound hair,follicle
R3770 T13413 T13411 prep of,Comparison
R3771 T13282 T13280 compound follicle,bulb
R3772 T13414 T13415 advmod immunochemically,stained
R3773 T13415 T13416 amod stained,sections
R3774 T13416 T13413 pobj sections,of
R3775 T13283 T13280 acl containing,bulb
R3776 T13417 T13416 amod serial,sections
R3777 T13418 T13419 mark that,found
R3778 T13284 T13285 amod proliferating,cells
R3779 T13285 T13283 dobj cells,containing
R3780 T13419 T13412 ccomp found,showed
R3781 T13286 T13276 punct .,becoming
R3782 T13420 T13421 det these,stainings
R3783 T13421 T13419 nsubjpass stainings,found
R3784 T13422 T13421 amod intense,stainings
R3785 T13288 T13289 advmod Hence,seems
R3786 T13423 T13424 amod cytosolic,β
R3787 T13424 T13421 nmod β,stainings
R3788 T13425 T13424 punct -,β
R3789 T13290 T13289 punct ", ",seems
R3790 T13426 T13424 appos catenin,β
R3791 T13427 T13419 auxpass were,found
R3792 T13428 T13419 advmod usually,found
R3793 T13429 T13419 prep in,found
R3794 T13291 T13289 prep despite,seems
R3795 T13430 T13431 preconj either,epidermis
R3796 T13431 T13429 pobj epidermis,in
R3797 T13292 T13293 det the,histology
R3798 T13432 T13433 npadvmod K14,positive
R3799 T13433 T13431 amod positive,epidermis
R3800 T13434 T13433 punct -,positive
R3801 T13293 T13291 pobj histology,despite
R3802 T13435 T13436 npadvmod K1,negative
R3803 T13436 T13431 amod negative,epidermis
R3804 T13294 T13293 amod abnormal,histology
R3805 T13437 T13436 punct -,negative
R3806 T13438 T13431 amod basal,epidermis
R3807 T13439 T13431 cc or,epidermis
R3808 T13295 T13293 prep in,histology
R3809 T13440 T13441 npadvmod K14,positive
R3810 T13441 T13443 amod positive,cells
R3811 T13442 T13441 punct -,positive
R3812 T13443 T13431 conj cells,epidermis
R3813 T13444 T13445 npadvmod K6,negative
R3814 T13445 T13443 amod negative,cells
R3815 T13296 T13297 det the,skin
R3816 T13446 T13445 punct -,negative
R3817 T13447 T13443 amod basal,cells
R3818 T13448 T13443 compound ORS,cells
R3819 T13297 T13295 pobj skin,in
R3820 T13449 T13419 punct ", ",found
R3821 T13450 T13419 cc and,found
R3822 T13298 T13297 amod mutant,skin
R3823 T13451 T13452 auxpass are,surrounded
R3824 T13452 T13419 conj surrounded,found
R3825 T13453 T13452 agent by,surrounded
R3826 T13299 T13289 punct ", ",seems
R3827 T13454 T13455 amod proliferating,cells
R3828 T13455 T13453 pobj cells,by
R3829 T13456 T13412 punct .,showed
R3830 T13300 T13289 nsubj proliferation,seems
R3831 T13458 T13459 aux To,determine
R3832 T13301 T13302 aux to,confined
R3833 T13459 T13460 advcl determine,examined
R3834 T13461 T13462 det the,initiation
R3835 T13302 T13289 xcomp confined,seems
R3836 T13303 T13302 auxpass be,confined
R3837 T13304 T13302 prep to,confined
R3838 T13305 T13306 npadvmod bulb,like
R3839 T13462 T13459 dobj initiation,determine
R3840 T13463 T13462 prep of,initiation
R3841 T13306 T13308 amod like,structures
R3842 T13464 T13465 compound hair,follicle
R3843 T13465 T13466 compound follicle,morphogenesis
R3844 T13466 T13463 pobj morphogenesis,of
R3845 T13307 T13306 punct -,like
R3846 T13467 T13459 prep in,determine
R3847 T13468 T13469 det these,mutants
R3848 T13308 T13304 pobj structures,to
R3849 T13469 T13467 pobj mutants,in
R3850 T13470 T13460 punct ", ",examined
R3851 T13471 T13460 nsubj we,examined
R3852 T13309 T13302 prep as,confined
R3853 T13472 T13473 det the,pattern
R3854 T13473 T13460 dobj pattern,examined
R3855 T13310 T13309 prep in,as
R3856 T13474 T13473 compound expression,pattern
R3857 T13475 T13473 prep of,pattern
R3858 T13476 T13477 compound Sonic,hedgehog
R3859 T13311 T13312 det the,skin
R3860 T13477 T13475 pobj hedgehog,of
R3861 T13478 T13477 punct (,hedgehog
R3862 T13479 T13477 appos Shh,hedgehog
R3863 T13480 T13477 punct ),hedgehog
R3864 T13481 T13477 punct ", ",hedgehog
R3865 T13482 T13483 det a,factor
R3866 T13312 T13310 pobj skin,in
R3867 T13483 T13477 appos factor,hedgehog
R3868 T13484 T13483 acl expressed,factor
R3869 T13485 T13484 prep in,expressed
R3870 T13313 T13312 amod normal,skin
R3871 T13486 T13487 compound hair,bulbs
R3872 T13487 T13485 pobj bulbs,in
R3873 T13314 T13315 punct (,4G
R3874 T13488 T13487 prep in,bulbs
R3875 T13489 T13490 amod embryonic,skin
R3876 T13490 T13488 pobj skin,in
R3877 T13315 T13302 parataxis 4G,confined
R3878 T13491 T13492 punct (,Figure
R3879 T13492 T13460 parataxis Figure,examined
R3880 T13316 T13315 compound Figure,4G
R3881 T13493 T13492 nummod 5,Figure
R3882 T13494 T13492 punct ),Figure
R3883 T13495 T13460 punct .,examined
R3884 T13317 T13315 cc and,4G
R3885 T13497 T13498 det The,morphogenesis
R3886 T13318 T13315 conj 4G,4G
R3887 T13498 T13502 nsubj morphogenesis,is
R3888 T13499 T13498 amod aberrant,morphogenesis
R3889 T13500 T13501 compound hair,follicle
R3890 T13319 T13318 punct ′,4G
R3891 T13501 T13498 compound follicle,morphogenesis
R3892 T13503 T13502 acomp evident,is
R3893 T13320 T13315 punct ),4G
R3894 T13504 T13505 advmod as,early
R3895 T13505 T13502 advmod early,is
R3896 T13321 T13289 punct .,seems
R3897 T13506 T13505 prep as,early
R3898 T13507 T13506 pobj E14.5,as
R3899 T13323 T13324 det The,locations
R3900 T13508 T13502 prep in,is
R3901 T13324 T13326 nsubj locations,were
R3902 T13509 T13510 amod mutant,skin
R3903 T13510 T13508 pobj skin,in
R3904 T13511 T13510 amod embryonic,skin
R3905 T13325 T13324 amod exact,locations
R3906 T13512 T13502 punct ", ",is
R3907 T13513 T13502 prep by,is
R3908 T13327 T13324 prep of,locations
R3909 T13514 T13515 amod multiple,expression
R3910 T13515 T13513 pobj expression,by
R3911 T13516 T13515 amod apolarized,expression
R3912 T13517 T13515 prep of,expression
R3913 T13328 T13329 compound hair,follicle
R3914 T13518 T13517 pobj Shh,of
R3915 T13519 T13515 prep throughout,expression
R3916 T13520 T13521 det the,epidermis
R3917 T13521 T13519 pobj epidermis,throughout
R3918 T13522 T13523 punct (,5B
R3919 T13329 T13330 compound follicle,bulbs
R3920 T13523 T13502 parataxis 5B,is
R3921 T13524 T13523 compound Figure,5B
R3922 T13525 T13523 punct ),5B
R3923 T13330 T13327 pobj bulbs,of
R3924 T13526 T13502 punct ", ",is
R3925 T13527 T13528 mark whereas,was
R3926 T13528 T13502 advcl was,is
R3927 T13331 T13326 neg not,were
R3928 T13529 T13528 nsubj that,was
R3929 T13530 T13529 prep of,that
R3930 T13531 T13532 compound control,embryos
R3931 T13332 T13333 advmod as,easy
R3932 T13532 T13530 pobj embryos,of
R3933 T13533 T13534 advmod well,polarized
R3934 T13534 T13528 acomp polarized,was
R3935 T13535 T13534 cc and,polarized
R3936 T13333 T13326 acomp easy,were
R3937 T13536 T13537 advmod regularly,spaced
R3938 T13537 T13534 conj spaced,polarized
R3939 T13538 T13539 punct (,5A
R3940 T13334 T13335 aux to,define
R3941 T13539 T13528 parataxis 5A,was
R3942 T13540 T13539 compound Figure,5A
R3943 T13541 T13539 punct ),5A
R3944 T13335 T13333 advcl define,easy
R3945 T13542 T13502 punct .,is
R3946 T13336 T13326 prep for,were
R3947 T13544 T13545 prep With,invaginate
R3948 T13546 T13544 pobj development,With
R3949 T13337 T13338 det some,follicles
R3950 T13547 T13545 punct ", ",invaginate
R3951 T13548 T13549 compound control,mouse
R3952 T13338 T13336 pobj follicles,for
R3953 T13549 T13550 compound mouse,follicles
R3954 T13550 T13545 nsubj follicles,invaginate
R3955 T13551 T13550 compound hair,follicles
R3956 T13552 T13545 advmod downward,invaginate
R3957 T13339 T13338 amod mutant,follicles
R3958 T13553 T13545 prep in,invaginate
R3959 T13554 T13555 det a,manner
R3960 T13340 T13326 prep due,were
R3961 T13555 T13553 pobj manner,in
R3962 T13556 T13555 amod polarized,manner
R3963 T13557 T13558 punct (,5C
R3964 T13341 T13340 pcomp to,due
R3965 T13558 T13545 parataxis 5C,invaginate
R3966 T13559 T13558 compound Figure,5C
R3967 T13560 T13558 punct ),5C
R3968 T13561 T13545 punct ", ",invaginate
R3969 T13562 T13563 mark whereas,were
R3970 T13563 T13545 advcl were,invaginate
R3971 T13564 T13563 nsubj those,were
R3972 T13342 T13343 poss their,structures
R3973 T13565 T13564 prep of,those
R3974 T13566 T13567 amod mutant,embryos
R3975 T13567 T13565 pobj embryos,of
R3976 T13343 T13340 pobj structures,due
R3977 T13344 T13343 amod disorganized,structures
R3978 T13345 T13326 punct .,were
R3979 T13347 T13348 advmod Interestingly,observed
R3980 T13568 T13569 advmod completely,irregular
R3981 T13349 T13348 punct ", ",observed
R3982 T13569 T13563 acomp irregular,were
R3983 T13570 T13569 cc and,irregular
R3984 T13571 T13569 conj apolarized,irregular
R3985 T13572 T13573 punct (,5D
R3986 T13350 T13348 prep in,observed
R3987 T13573 T13563 parataxis 5D,were
R3988 T13574 T13573 compound Figure,5D
R3989 T13351 T13352 det the,skin
R3990 T13575 T13573 punct ),5D
R3991 T13576 T13545 punct .,invaginate
R3992 T13352 T13350 pobj skin,in
R3993 T13578 T13579 nsubjpass It,noted
R3994 T13353 T13352 amod mutant,skin
R3995 T13580 T13579 auxpass was,noted
R3996 T13581 T13579 advmod also,noted
R3997 T13582 T13583 mark that,was
R3998 T13354 T13348 punct ", ",observed
R3999 T13355 T13348 prep in,observed
R4000 T13583 T13579 ccomp was,noted
R4001 T13356 T13355 pobj addition,in
R4002 T13584 T13585 det the,size
R4003 T13585 T13583 nsubj size,was
R4004 T13586 T13585 prep of,size
R4005 T13674 T13673 punct -,catenin
R4006 T13587 T13588 det each,follicle
R4007 T13588 T13586 pobj follicle,of
R4008 T13589 T13588 punct “,follicle
R4009 T13590 T13588 nmod budding,follicle
R4010 T13675 T13668 prep in,pattern
R4011 T13591 T13588 punct ”,follicle
R4012 T13592 T13585 punct ", ",size
R4013 T13676 T13675 pobj embryos,in
R4014 T13593 T13594 mark as,detected
R4015 T13594 T13585 advcl detected,size
R4016 T13595 T13594 prep by,detected
R4017 T13596 T13597 compound Shh,expression
R4018 T13597 T13595 pobj expression,by
R4019 T13598 T13583 punct ", ",was
R4020 T13677 T13670 advmod clearly,demonstrated
R4021 T13599 T13583 acomp variable,was
R4022 T13600 T13601 punct (,5D
R4023 T13678 T13679 det the,formation
R4024 T13601 T13583 parataxis 5D,was
R4025 T13602 T13601 compound Figure,5D
R4026 T13603 T13601 punct ),5D
R4027 T13679 T13670 dobj formation,demonstrated
R4028 T13604 T13579 punct .,noted
R4029 T13680 T13679 prep of,formation
R4030 T13606 T13607 det The,intensity
R4031 T13607 T13608 nsubj intensity,was
R4032 T13609 T13607 prep of,intensity
R4033 T13610 T13611 compound Shh,staining
R4034 T13611 T13609 pobj staining,of
R4035 T13681 T13682 amod regular,arrays
R4036 T13612 T13608 advmod generally,was
R4037 T13613 T13608 acomp stronger,was
R4038 T13682 T13680 pobj arrays,of
R4039 T13614 T13608 prep in,was
R4040 T13615 T13616 amod mutant,skin
R4041 T13616 T13614 pobj skin,in
R4042 T13683 T13682 prep of,arrays
R4043 T13617 T13608 prep than,was
R4044 T13618 T13617 prep in,than
R4045 T13619 T13620 det the,skin
R4046 T13684 T13685 compound hair,placodes
R4047 T13620 T13618 pobj skin,in
R4048 T13621 T13620 amod normal,skin
R4049 T13622 T13608 punct .,was
R4050 T13685 T13683 pobj placodes,of
R4051 T13624 T13625 det The,initiation
R4052 T13625 T13627 nsubj initiation,was
R4053 T13686 T13670 prep in,demonstrated
R4054 T13626 T13625 amod aberrant,initiation
R4055 T13687 T13688 det the,skin
R4056 T13628 T13625 prep of,initiation
R4057 T13629 T13630 amod multiple,placodes
R4058 T13630 T13628 pobj placodes,of
R4059 T13631 T13630 compound hair,placodes
R4060 T13688 T13686 pobj skin,in
R4061 T13632 T13625 prep during,initiation
R4062 T13633 T13634 amod early,morphogenesis
R4063 T13689 T13688 amod normal,skin
R4064 T13634 T13632 pobj morphogenesis,during
R4065 T13635 T13636 compound hair,follicle
R4066 T13636 T13634 compound follicle,morphogenesis
R4067 T13637 T13627 advmod also,was
R4068 T13638 T13627 acomp evident,was
R4069 T13639 T13627 prep by,was
R4070 T13640 T13641 det the,mount
R4071 T13641 T13639 pobj mount,by
R4072 T13690 T13688 amod embryonic,skin
R4073 T13642 T13641 amod whole,mount
R4074 T13643 T13641 punct -,mount
R4075 T13644 T13645 advmod in,situ
R4076 T13645 T13646 amod situ,hybridization
R4077 T13691 T13692 punct (,5E
R4078 T13646 T13641 appos hybridization,mount
R4079 T13647 T13646 punct (,hybridization
R4080 T13648 T13646 appos ISH,hybridization
R4081 T13649 T13641 punct ),mount
R4082 T13692 T13670 parataxis 5E,demonstrated
R4083 T13650 T13641 prep of,mount
R4084 T13651 T13652 nmod E15.5,embryos
R4085 T13652 T13650 pobj embryos,of
R4086 T13693 T13692 compound Figure,5E
R4087 T13653 T13652 amod mutant,embryos
R4088 T13654 T13641 prep for,mount
R4089 T13694 T13692 cc and,5E
R4090 T13655 T13656 compound β,catenin
R4091 T13656 T13654 pobj catenin,for
R4092 T13657 T13656 punct -,catenin
R4093 T13658 T13659 punct (,5F
R4094 T13695 T13692 conj 5E,5E
R4095 T13659 T13627 parataxis 5F,was
R4096 T13660 T13659 compound Figure,5F
R4097 T13696 T13695 punct ′,5E
R4098 T13661 T13659 cc and,5F
R4099 T13662 T13659 conj 5F,5F
R4100 T13663 T13662 punct ′,5F
R4101 T13664 T13659 punct ),5F
R4102 T13697 T13692 punct ),5E
R4103 T13665 T13627 punct .,was
R4104 T13667 T13668 det The,pattern
R4105 T13698 T13670 punct ", ",demonstrated
R4106 T13668 T13670 nsubj pattern,demonstrated
R4107 T13669 T13668 compound expression,pattern
R4108 T13699 T13670 cc but,demonstrated
R4109 T13671 T13668 prep of,pattern
R4110 T13672 T13673 compound β,catenin
R4111 T13700 T13701 amod such,patterning
R4112 T13673 T13671 pobj catenin,of
R4113 T13701 T13703 nsubjpass patterning,lost
R4114 T13702 T13701 amod regular,patterning
R4115 T13703 T13670 conj lost,demonstrated
R4116 T13704 T13703 auxpass was,lost
R4117 T13705 T13703 punct ", ",lost
R4118 T13780 T13779 compound Figure,5G
R4119 T13706 T13703 cc and,lost
R4120 T13781 T13779 punct ),5G
R4121 T13782 T13764 punct ", ",found
R4122 T13783 T13764 nsubj we,found
R4123 T13784 T13764 advmod also,found
R4124 T13785 T13786 amod ectopic,placodes
R4125 T13707 T13708 advmod often,initiated
R4126 T13786 T13764 dobj placodes,found
R4127 T13787 T13788 advmod irregularly,sized
R4128 T13788 T13786 amod sized,placodes
R4129 T13708 T13703 conj initiated,lost
R4130 T13789 T13788 cc and,sized
R4131 T13790 T13788 conj spaced,sized
R4132 T13791 T13786 compound hair,placodes
R4133 T13709 T13710 advmod tightly,clustered
R4134 T13792 T13764 punct ", ",found
R4135 T13793 T13764 advcl indicating,found
R4136 T13710 T13711 amod clustered,placodes
R4137 T13794 T13795 mark that,have
R4138 T13795 T13793 ccomp have,indicating
R4139 T13796 T13797 det the,footpads
R4140 T13711 T13708 nsubjpass placodes,initiated
R4141 T13797 T13795 nsubj footpads,have
R4142 T13798 T13795 advmod still,have
R4143 T13799 T13800 det the,potential
R4144 T13712 T13711 amod abnormal,placodes
R4145 T13800 T13795 dobj potential,have
R4146 T13801 T13802 aux to,form
R4147 T13713 T13711 compound hair,placodes
R4148 T13802 T13800 acl form,potential
R4149 T13803 T13804 compound hair,placodes
R4150 T13804 T13802 dobj placodes,form
R4151 T13714 T13708 auxpass were,initiated
R4152 T13805 T13802 prep in,form
R4153 T13806 T13807 det the,absence
R4154 T13807 T13805 pobj absence,in
R4155 T13715 T13708 prep in,initiated
R4156 T13808 T13807 prep of,absence
R4157 T13809 T13810 det the,gene
R4158 T13810 T13808 pobj gene,of
R4159 T13716 T13717 amod mutant,embryonic
R4160 T13811 T13810 compound Apc,gene
R4161 T13812 T13813 punct (,5H
R4162 T13813 T13764 parataxis 5H,found
R4163 T13717 T13718 amod embryonic,skin
R4164 T13814 T13813 compound Figure,5H
R4165 T13815 T13813 punct ),5H
R4166 T13718 T13715 pobj skin,in
R4167 T13816 T13764 punct .,found
R4168 T13818 T13819 det These,results
R4169 T13819 T13820 nsubj results,suggest
R4170 T13719 T13720 punct (,5F
R4171 T13821 T13820 advmod collectively,suggest
R4172 T13720 T13708 parataxis 5F,initiated
R4173 T13822 T13823 mark that,take
R4174 T13823 T13820 ccomp take,suggest
R4175 T13824 T13825 det the,differentiation
R4176 T13825 T13823 nsubj differentiation,take
R4177 T13826 T13825 amod terminal,differentiation
R4178 T13827 T13823 aux does,take
R4179 T13721 T13720 compound Figure,5F
R4180 T13828 T13823 dobj place,take
R4181 T13829 T13823 advmod normally,take
R4182 T13830 T13823 prep in,take
R4183 T13831 T13832 det the,skin
R4184 T13722 T13720 punct ′,5F
R4185 T13832 T13830 pobj skin,in
R4186 T13833 T13832 amod mutant,skin
R4187 T13723 T13720 punct ),5F
R4188 T13834 T13823 punct ", ",take
R4189 T13835 T13823 cc but,take
R4190 T13836 T13837 nsubjpass initiation,accompanied
R4191 T13724 T13703 punct .,lost
R4192 T13726 T13727 amod Aberrant,placodes
R4193 T13837 T13823 conj accompanied,take
R4194 T13838 T13836 prep of,initiation
R4195 T13839 T13840 amod embryonic,morphogenesis
R4196 T13840 T13838 pobj morphogenesis,of
R4197 T13727 T13729 nsubj placodes,were
R4198 T13841 T13842 compound hair,follicle
R4199 T13842 T13840 compound follicle,morphogenesis
R4200 T13728 T13727 compound hair,placodes
R4201 T13843 T13837 auxpass is,accompanied
R4202 T13844 T13837 advmod severely,accompanied
R4203 T13845 T13837 aux disrupted,accompanied
R4204 T13846 T13837 punct ", ",accompanied
R4205 T13730 T13729 advmod also,were
R4206 T13847 T13837 agent by,accompanied
R4207 T13848 T13849 det a,morphogenesis
R4208 T13849 T13847 pobj morphogenesis,by
R4209 T13850 T13849 amod continuous,morphogenesis
R4210 T13731 T13729 acomp evident,were
R4211 T13851 T13849 amod ectopic,morphogenesis
R4212 T13852 T13853 compound hair,follicle
R4213 T13732 T13729 prep throughout,were
R4214 T13853 T13849 compound follicle,morphogenesis
R4215 T13854 T13837 prep in,accompanied
R4216 T13855 T13856 amod postnatal,skin
R4217 T13733 T13734 det the,surface
R4218 T13856 T13854 pobj skin,in
R4219 T13857 T13856 amod mutant,skin
R4220 T13734 T13732 pobj surface,throughout
R4221 T13858 T13820 punct .,suggest
R4222 T13735 T13734 compound skin,surface
R4223 T13736 T13734 prep of,surface
R4224 T13737 T13736 pobj limbs,of
R4225 T13738 T13729 prep in,were
R4226 T13739 T13740 compound E15.5,mutants
R4227 T13740 T13738 pobj mutants,in
R4228 T13741 T13742 punct (,5F
R4229 T13742 T13729 parataxis 5F,were
R4230 T13743 T13742 compound Figure,5F
R4231 T13744 T13742 punct ),5F
R4232 T13745 T13729 punct ", ",were
R4233 T13746 T13747 mark whereas,formed
R4234 T13747 T13729 advcl formed,were
R4235 T13748 T13747 nsubj those,formed
R4236 T13749 T13748 prep of,those
R4237 T13750 T13751 det the,embryos
R4238 T13751 T13749 pobj embryos,of
R4239 T13752 T13751 compound control,embryos
R4240 T13753 T13747 aux had,formed
R4241 T13754 T13755 neg not,yet
R4242 T13755 T13747 advmod yet,formed
R4243 T13756 T13757 punct (,5E
R4244 T13757 T13747 parataxis 5E,formed
R4245 T13758 T13757 compound Figure,5E
R4246 T13759 T13757 punct ),5E
R4247 T13760 T13729 punct .,were
R4248 T13762 T13763 advmod Most,interestingly
R4249 T13763 T13764 advmod interestingly,found
R4250 T13765 T13764 punct ", ",found
R4251 T13766 T13764 prep in,found
R4252 T13767 T13768 det the,footpads
R4253 T13768 T13766 pobj footpads,in
R4254 T13769 T13768 amod mutant,footpads
R4255 T13770 T13768 punct ", ",footpads
R4256 T13771 T13772 advmod where,form
R4257 T13772 T13768 relcl form,footpads
R4258 T13773 T13774 compound hair,placodes
R4259 T13774 T13772 nsubj placodes,form
R4260 T13775 T13772 aux do,form
R4261 T13776 T13772 neg not,form
R4262 T13777 T13772 advmod normally,form
R4263 T13778 T13779 punct (,5G
R4264 T13779 T13772 parataxis 5G,form
R4273 T14506 T14505 prep of,Effects
R4274 T14507 T14508 compound K14,cre
R4275 T14508 T14510 npadvmod cre,Driven
R4276 T14509 T14508 punct -,cre
R4277 T14510 T14512 amod Driven,Loss
R4278 T14511 T14510 punct –,Driven
R4279 T14512 T14506 pobj Loss,of
R4280 T14513 T14512 prep of,Loss
R4281 T14514 T14513 pobj Apc,of
R4282 T14515 T14505 prep in,Effects
R4283 T14516 T14517 amod Other,Appendages
R4284 T14517 T14515 pobj Appendages,in
R4285 T14518 T14517 amod Epidermal,Appendages
R4286 T14520 T14521 advcl Similar,affected
R4287 T14522 T14520 prep to,Similar
R4288 T14523 T14524 det the,biology
R4289 T14524 T14522 pobj biology,to
R4290 T14525 T14524 prep of,biology
R4291 T14526 T14527 compound hair,follicles
R4292 T14527 T14525 pobj follicles,of
R4293 T14528 T14521 punct ", ",affected
R4294 T14529 T14530 compound K14,cre
R4295 T14530 T14532 npadvmod cre,driven
R4296 T14531 T14530 punct -,cre
R4297 T14532 T14534 amod driven,loss
R4298 T14533 T14532 punct –,driven
R4299 T14534 T14521 nsubj loss,affected
R4300 T14535 T14534 prep of,loss
R4301 T14536 T14535 pobj Apc,of
R4302 T14537 T14521 advmod also,affected
R4303 T14538 T14539 det the,development
R4304 T14539 T14521 dobj development,affected
R4305 T14540 T14539 prep of,development
R4306 T14541 T14542 amod other,appendages
R4307 T14542 T14540 pobj appendages,of
R4308 T14543 T14542 amod epidermal,appendages
R4309 T14544 T14545 dep that,depend
R4310 T14545 T14542 relcl depend,appendages
R4311 T14546 T14545 prep on,depend
R4312 T14547 T14548 amod epithelial,mesenchymal
R4313 T14548 T14550 amod mesenchymal,interactions
R4314 T14549 T14548 punct –,mesenchymal
R4315 T14550 T14546 pobj interactions,on
R4316 T14551 T14545 prep for,depend
R4317 T14552 T14553 poss their,formation
R4318 T14553 T14551 pobj formation,for
R4319 T14554 T14521 punct .,affected
R4320 T14556 T14557 det The,striking
R4321 T14557 T14559 nsubj striking,was
R4322 T14558 T14557 advmod most,striking
R4323 T14560 T14557 prep of,striking
R4324 T14561 T14560 pobj these,of
R4325 T14562 T14563 amod dental,dysplasia
R4326 T14563 T14559 attr dysplasia,was
R4327 T14564 T14565 punct (,4K
R4328 T14565 T14559 parataxis 4K,was
R4329 T14566 T14565 compound Figure,4K
R4330 T14567 T14568 punct –,4R
R4331 T14568 T14565 prep 4R,4K
R4332 T14569 T14565 punct ),4K
R4333 T14570 T14559 punct .,was
R4334 T14572 T14573 compound Tooth,development
R4335 T14573 T14574 nsubjpass development,initiated
R4336 T14575 T14574 auxpass is,initiated
R4337 T14576 T14574 advmod normally,initiated
R4338 T14577 T14574 prep between,initiated
R4339 T14578 T14577 pobj E11,between
R4340 T14579 T14578 cc and,E11
R4341 T14580 T14578 conj E12,E11
R4342 T14581 T14574 prep by,initiated
R4343 T14582 T14581 pobj invagination,by
R4344 T14583 T14582 prep of,invagination
R4345 T14584 T14585 advmod ectodermally,derived
R4346 T14585 T14586 amod derived,epithelium
R4347 T14586 T14583 pobj epithelium,of
R4348 T14587 T14586 amod oral,epithelium
R4349 T14588 T14582 prep into,invagination
R4350 T14589 T14590 det the,mesenchyme
R4351 T14590 T14588 pobj mesenchyme,into
R4352 T14591 T14590 amod underlying,mesenchyme
R4353 T14592 T14593 amod cranial,crest
R4354 T14593 T14595 npadvmod crest,derived
R4355 T14594 T14593 amod neural,crest
R4356 T14595 T14590 amod derived,mesenchyme
R4357 T14596 T14595 punct –,derived
R4358 T14597 T14574 punct ", ",initiated
R4359 T14598 T14574 advcl generating,initiated
R4360 T14599 T14600 det a,germ
R4361 T14600 T14598 dobj germ,generating
R4362 T14601 T14600 amod tooth,germ
R4363 T14602 T14574 punct .,initiated
R4364 T14604 T14605 prep Despite,revealed
R4365 T14606 T14607 det the,phenotype
R4366 T14607 T14604 pobj phenotype,Despite
R4367 T14608 T14609 advmod grossly,toothless
R4368 T14609 T14607 amod toothless,phenotype
R4369 T14610 T14607 prep of,phenotype
R4370 T14611 T14612 compound KA,mutants
R4371 T14612 T14610 pobj mutants,of
R4372 T14613 T14605 punct ", ",revealed
R4373 T14614 T14615 amod histological,analysis
R4374 T14615 T14605 nsubj analysis,revealed
R4375 T14616 T14615 prep of,analysis
R4376 T14617 T14618 poss their,cavities
R4377 T14618 T14616 pobj cavities,of
R4378 T14619 T14618 amod oral,cavities
R4379 T14620 T14621 det the,formation
R4380 T14621 T14605 dobj formation,revealed
R4381 T14622 T14621 prep of,formation
R4382 T14623 T14624 amod multiple,buds
R4383 T14624 T14622 pobj buds,of
R4384 T14625 T14624 amod tooth,buds
R4385 T14626 T14605 prep at,revealed
R4386 T14627 T14628 det each,location
R4387 T14628 T14626 pobj location,at
R4388 T14629 T14605 punct .,revealed
R4389 T14631 T14632 det These,teeth
R4390 T14632 T14634 nsubj teeth,failed
R4391 T14633 T14632 amod aberrant,teeth
R4392 T14635 T14634 advmod obviously,failed
R4393 T14636 T14637 aux to,grow
R4394 T14637 T14634 xcomp grow,failed
R4395 T14638 T14637 prt out,grow
R4396 T14639 T14637 prep during,grow
R4397 T14640 T14641 det the,transition
R4398 T14641 T14639 pobj transition,during
R4399 T14642 T14641 amod dietary,transition
R4400 T14643 T14641 prep from,transition
R4401 T14644 T14643 pobj milk,from
R4402 T14645 T14641 prep to,transition
R4403 T14646 T14647 amod solid,food
R4404 T14647 T14645 pobj food,to
R4405 T14648 T14634 punct .,failed
R4406 T14650 T14651 advcl Analogous,detected
R4407 T14652 T14650 prep to,Analogous
R4408 T14653 T14654 det the,patterns
R4409 T14654 T14652 pobj patterns,to
R4410 T14655 T14654 compound expression,patterns
R4411 T14656 T14654 prep of,patterns
R4412 T14657 T14656 pobj K14,of
R4413 T14658 T14657 cc and,K14
R4414 T14659 T14660 compound β,catenin
R4415 T14660 T14657 conj catenin,K14
R4416 T14661 T14660 punct -,catenin
R4417 T14662 T14654 prep in,patterns
R4418 T14663 T14664 det the,skin
R4419 T14664 T14662 pobj skin,in
R4420 T14665 T14664 amod normal,skin
R4421 T14666 T14651 punct ", ",detected
R4422 T14667 T14668 amod diffuse,expression
R4423 T14668 T14651 nsubjpass expression,detected
R4424 T14669 T14670 npadvmod membrane,bound
R4425 T14670 T14668 amod bound,expression
R4426 T14671 T14670 punct -,bound
R4427 T14672 T14668 prep of,expression
R4428 T14673 T14674 compound β,catenin
R4429 T14674 T14672 pobj catenin,of
R4430 T14675 T14674 punct -,catenin
R4431 T14676 T14651 auxpass was,detected
R4432 T14677 T14651 prep in,detected
R4433 T14678 T14679 npadvmod K14,expressing
R4434 T14679 T14681 amod expressing,epithelium
R4435 T14680 T14679 punct -,expressing
R4436 T14681 T14677 pobj epithelium,in
R4437 T14682 T14681 amod oral,epithelium
R4438 T14683 T14681 cc and,epithelium
R4439 T14684 T14681 conj ameloblasts,epithelium
R4440 T14685 T14681 prep of,epithelium
R4441 T14686 T14687 amod normal,mice
R4442 T14687 T14685 pobj mice,of
R4443 T14688 T14651 punct .,detected
R4444 T14690 T14691 prep In,showed
R4445 T14692 T14690 pobj mutants,In
R4446 T14693 T14691 punct ", ",showed
R4447 T14694 T14691 nsubj some,showed
R4448 T14695 T14694 prep of,some
R4449 T14696 T14697 det the,cells
R4450 T14697 T14695 pobj cells,of
R4451 T14698 T14699 npadvmod K14,expressing
R4452 T14699 T14697 amod expressing,cells
R4453 T14700 T14699 punct -,expressing
R4454 T14701 T14691 advmod also,showed
R4455 T14702 T14703 amod strong,staining
R4456 T14703 T14691 dobj staining,showed
R4457 T14704 T14705 amod cytosolic,β
R4458 T14705 T14703 nmod β,staining
R4459 T14706 T14705 punct /,β
R4460 T14707 T14705 amod nuclear,β
R4461 T14708 T14705 punct -,β
R4462 T14709 T14705 appos catenin,β
R4463 T14710 T14691 punct ", ",showed
R4464 T14711 T14712 mark as,observed
R4465 T14712 T14691 advcl observed,showed
R4466 T14713 T14712 prep in,observed
R4467 T14714 T14715 det the,skin
R4468 T14715 T14713 pobj skin,in
R4469 T14716 T14715 amod mutant,skin
R4470 T14717 T14718 punct (,4Q
R4471 T14718 T14691 parataxis 4Q,showed
R4472 T14719 T14718 compound Figure,4Q
R4473 T14720 T14718 punct ", ",4Q
R4474 T14721 T14718 conj 4Q,4Q
R4475 T14722 T14721 punct ′,4Q
R4476 T14723 T14721 punct ", ",4Q
R4477 T14724 T14721 cc and,4Q
R4478 T14725 T14721 conj 4R,4Q
R4479 T14726 T14718 punct ),4Q
R4480 T14727 T14691 punct .,showed
R4481 T14729 T14730 nsubj Initiation,was
R4482 T14731 T14729 prep of,Initiation
R4483 T14732 T14733 amod ectopic,buds
R4484 T14733 T14731 pobj buds,of
R4485 T14734 T14733 amod tooth,buds
R4486 T14735 T14729 prep in,Initiation
R4487 T14736 T14737 det the,mice
R4488 T14737 T14735 pobj mice,in
R4489 T14738 T14737 amod mutant,mice
R4490 T14739 T14730 acomp evident,was
R4491 T14740 T14730 prep at,was
R4492 T14741 T14740 pobj E15.5,at
R4493 T14742 T14730 prep by,was
R4494 T14743 T14744 amod extra,dots
R4495 T14744 T14742 pobj dots,by
R4496 T14745 T14744 prep of,dots
R4497 T14746 T14747 compound Shh,expression
R4498 T14747 T14745 pobj expression,of
R4499 T14748 T14744 amod adjacent,dots
R4500 T14749 T14748 prep to,adjacent
R4501 T14750 T14751 det the,teeth
R4502 T14751 T14749 pobj teeth,to
R4503 T14752 T14751 amod primary,teeth
R4504 T14753 T14754 punct (,shown
R4505 T14754 T14730 parataxis shown,was
R4506 T14755 T14754 nsubj data,shown
R4507 T14756 T14754 neg not,shown
R4508 T14757 T14754 punct ),shown
R4509 T14758 T14730 punct .,was
R4510 T14760 T14761 nsubj Loss,leads
R4511 T14762 T14760 prep of,Loss
R4512 T14763 T14762 pobj Apc,of
R4513 T14764 T14761 advmod also,leads
R4514 T14765 T14761 prep to,leads
R4515 T14766 T14765 pobj hyperplasia,to
R4516 T14767 T14766 prep in,hyperplasia
R4517 T14768 T14769 amod squamous,epithelia
R4518 T14769 T14767 pobj epithelia,in
R4519 T14770 T14769 prep of,epithelia
R4520 T14771 T14772 nmod cornea,glands
R4521 T14772 T14770 pobj glands,of
R4522 T14773 T14771 punct ", ",cornea
R4523 T14774 T14771 conj oral,cornea
R4524 T14775 T14774 punct ", ",oral
R4525 T14776 T14774 conj salivary,oral
R4526 T14777 T14776 punct ", ",salivary
R4527 T14778 T14776 cc and,salivary
R4528 T14779 T14776 conj Hardarian,salivary
R4529 T14780 T14781 punct (,data
R4530 T14781 T14761 meta data,leads
R4531 T14782 T14781 amod unpublished,data
R4532 T14783 T14781 punct ),data
R4533 T14784 T14761 punct .,leads
R4534 T14786 T14787 amod Squamous,metaplasia
R4535 T14787 T14788 nsubjpass metaplasia,observed
R4536 T14789 T14787 prep to,metaplasia
R4537 T14790 T14791 compound hair,follicle
R4538 T14791 T14792 npadvmod follicle,like
R4539 T14792 T14794 amod like,structures
R4540 T14793 T14792 punct –,like
R4541 T14794 T14789 pobj structures,to
R4542 T14795 T14787 punct ", ",metaplasia
R4543 T14796 T14797 amod ectopic,morphogenesis
R4544 T14797 T14787 appos morphogenesis,metaplasia
R4545 T14798 T14799 compound hair,follicle
R4546 T14799 T14797 compound follicle,morphogenesis
R4547 T14800 T14788 auxpass was,observed
R4548 T14801 T14788 advmod also,observed
R4549 T14802 T14788 prep in,observed
R4550 T14803 T14804 det these,epithelia
R4551 T14804 T14802 pobj epithelia,in
R4552 T14805 T14788 punct .,observed
R4564 T17241 T17242 compound K14,cre
R4565 T17242 T17244 npadvmod cre,Driven
R4566 T17243 T17242 punct -,cre
R4567 T17244 T17246 amod Driven,Loss
R4568 T17245 T17244 punct –,Driven
R4569 T17246 T17248 nsubj Loss,Results
R4570 T17247 T17246 compound Apc,Loss
R4571 T17249 T17248 prep in,Results
R4572 T17250 T17251 amod Hypoplastic,Athymic
R4573 T17251 T17253 amod Athymic,Mice
R4574 T17252 T17251 punct /,Athymic
R4575 T17253 T17249 pobj Mice,in
R4576 T17255 T17256 nsubj Thymus,is
R4577 T17257 T17258 det an,organ
R4578 T17258 T17256 attr organ,is
R4579 T17259 T17260 dep that,known
R4580 T17260 T17258 relcl known,organ
R4581 T17261 T17260 auxpass is,known
R4582 T17262 T17260 advmod also,known
R4583 T17263 T17264 aux to,have
R4584 T17264 T17260 xcomp have,known
R4585 T17265 T17266 compound K14,expression
R4586 T17266 T17264 dobj expression,have
R4587 T17267 T17268 punct [,16
R4588 T17268 T17258 parataxis 16,organ
R4589 T17269 T17268 punct ],16
R4590 T17270 T17256 punct .,is
R4591 T17272 T17273 nsubj It,represents
R4592 T17274 T17275 det the,organ
R4593 T17275 T17273 dobj organ,represents
R4594 T17276 T17275 amod primary,organ
R4595 T17277 T17275 amod lymphoid,organ
R4596 T17278 T17275 prep for,organ
R4597 T17279 T17280 compound thymocyte,development
R4598 T17280 T17278 pobj development,for
R4599 T17281 T17280 cc and,development
R4600 T17282 T17280 conj selection,development
R4601 T17283 T17273 punct .,represents
R4602 T17285 T17286 amod Distinct,population
R4603 T17286 T17287 nsubj population,mediates
R4604 T17288 T17286 prep of,population
R4605 T17289 T17288 pobj TECs,of
R4606 T17290 T17289 prep of,TECs
R4607 T17291 T17290 pobj cortex,of
R4608 T17292 T17291 cc and,cortex
R4609 T17293 T17291 conj medulla,cortex
R4610 T17294 T17287 dobj both,mediates
R4611 T17295 T17294 prep of,both
R4612 T17296 T17297 det these,functions
R4613 T17297 T17295 pobj functions,of
R4614 T17298 T17297 amod critical,functions
R4615 T17299 T17287 punct .,mediates
R4616 T17301 T17302 amod Cortical,subsets
R4617 T17302 T17306 nsubjpass subsets,characterized
R4618 T17303 T17301 cc and,Cortical
R4619 T17304 T17301 conj medullary,Cortical
R4620 T17305 T17302 compound TEC,subsets
R4621 T17307 T17306 auxpass are,characterized
R4622 T17308 T17306 agent by,characterized
R4623 T17309 T17310 amod differential,expression
R4624 T17310 T17308 pobj expression,by
R4625 T17311 T17310 prep of,expression
R4626 T17312 T17313 nummod four,species
R4627 T17313 T17311 pobj species,of
R4628 T17314 T17313 compound keratin,species
R4629 T17315 T17313 punct : ,species
R4630 T17316 T17313 appos K8,species
R4631 T17317 T17316 punct ", ",K8
R4632 T17318 T17316 conj K18,K8
R4633 T17319 T17318 punct ", ",K18
R4634 T17320 T17318 conj K5,K18
R4635 T17321 T17320 punct ", ",K5
R4636 T17322 T17320 cc and,K5
R4637 T17323 T17320 conj K14,K5
R4638 T17324 T17306 punct .,characterized
R4639 T17326 T17327 det The,thymus
R4640 T17327 T17329 nsubj thymus,is
R4641 T17328 T17327 amod normal,thymus
R4642 T17330 T17331 det a,organ
R4643 T17331 T17329 attr organ,is
R4644 T17332 T17331 amod lobulated,organ
R4645 T17333 T17331 amod lymphoid,organ
R4646 T17334 T17329 punct ", ",is
R4647 T17335 T17336 det each,lobule
R4648 T17336 T17337 nsubj lobule,showing
R4649 T17337 T17329 advcl showing,is
R4650 T17338 T17337 advmod clearly,showing
R4651 T17339 T17340 det the,compartments
R4652 T17340 T17337 dobj compartments,showing
R4653 T17341 T17340 nummod two,compartments
R4654 T17342 T17340 amod distinct,compartments
R4655 T17343 T17340 compound TEC,compartments
R4656 T17344 T17340 punct ", ",compartments
R4657 T17345 T17346 det an,cortex
R4658 T17346 T17340 appos cortex,compartments
R4659 T17347 T17346 amod outer,cortex
R4660 T17348 T17346 cc and,cortex
R4661 T17349 T17350 det an,medulla
R4662 T17350 T17346 conj medulla,cortex
R4663 T17351 T17350 amod inner,medulla
R4664 T17352 T17353 punct (,Figure
R4665 T17353 T17329 parataxis Figure,is
R4666 T17354 T17353 nummod 6,Figure
R4667 T17355 T17353 punct ),Figure
R4668 T17356 T17329 punct .,is
R4669 T17358 T17359 expl There,were
R4670 T17360 T17361 det no,differences
R4671 T17361 T17359 attr differences,were
R4672 T17362 T17361 amod major,differences
R4673 T17363 T17361 prep in,differences
R4674 T17364 T17365 det the,histology
R4675 T17365 T17363 pobj histology,in
R4676 T17366 T17365 prep of,histology
R4677 T17367 T17366 pobj thymus,of
R4678 T17368 T17359 prep between,were
R4679 T17369 T17370 det the,ages
R4680 T17370 T17368 pobj ages,between
R4681 T17371 T17370 appos P3,ages
R4682 T17372 T17371 prep to,P3
R4683 T17373 T17372 pobj P17,to
R4684 T17374 T17359 prep in,were
R4685 T17375 T17376 advmod phenotypically,normal
R4686 T17376 T17377 amod normal,littermates
R4687 T17377 T17374 pobj littermates,in
R4688 T17378 T17359 punct .,were
R4689 T17380 T17381 mark As,shown
R4690 T17381 T17382 advcl shown,formed
R4691 T17383 T17381 prep in,shown
R4692 T17384 T17385 det the,staining
R4693 T17385 T17383 pobj staining,in
R4694 T17386 T17385 nmod H,staining
R4695 T17387 T17386 cc &,H
R4696 T17388 T17386 conj E,H
R4697 T17389 T17385 prep of,staining
R4698 T17390 T17389 pobj thymus,of
R4699 T17391 T17382 punct ", ",formed
R4700 T17392 T17393 det the,cortex
R4701 T17393 T17382 nsubjpass cortex,formed
R4702 T17394 T17382 auxpass was,formed
R4703 T17395 T17382 prep of,formed
R4704 T17396 T17397 amod dense,tissue
R4705 T17397 T17395 pobj tissue,of
R4706 T17398 T17397 amod lymphoid,tissue
R4707 T17399 T17400 dep that,lacks
R4708 T17400 T17397 relcl lacks,tissue
R4709 T17401 T17400 dobj nodules,lacks
R4710 T17402 T17403 punct (,6A
R4711 T17403 T17382 parataxis 6A,formed
R4712 T17404 T17403 compound Figure,6A
R4713 T17405 T17403 punct ),6A
R4714 T17406 T17382 punct .,formed
R4715 T17408 T17409 mark Since,is
R4716 T17409 T17415 advcl is,stained
R4717 T17410 T17411 det the,stroma
R4718 T17411 T17409 nsubj stroma,is
R4719 T17412 T17411 prep of,stroma
R4720 T17413 T17414 det the,medulla
R4721 T17414 T17412 pobj medulla,of
R4722 T17416 T17417 advmod less,heavily
R4723 T17417 T17418 advmod heavily,infiltrated
R4724 T17418 T17409 acomp infiltrated,is
R4725 T17419 T17418 prep with,infiltrated
R4726 T17420 T17419 pobj lymphocytes,with
R4727 T17421 T17418 prep than,infiltrated
R4728 T17422 T17423 det the,cortex
R4729 T17423 T17421 pobj cortex,than
R4730 T17424 T17415 punct ", ",stained
R4731 T17425 T17426 det the,medulla
R4732 T17426 T17415 nsubj medulla,stained
R4733 T17427 T17428 advmod more,lightly
R4734 T17428 T17415 advmod lightly,stained
R4735 T17429 T17428 prep than,lightly
R4736 T17430 T17431 det the,cortex
R4737 T17431 T17429 pobj cortex,than
R4738 T17432 T17415 punct .,stained
R4739 T17434 T17435 prep In,retains
R4740 T17436 T17437 amod normal,mice
R4741 T17437 T17434 pobj mice,In
R4742 T17438 T17435 punct ", ",retains
R4743 T17439 T17440 det the,thymus
R4744 T17440 T17435 nsubj thymus,retains
R4745 T17441 T17442 poss its,size
R4746 T17442 T17435 dobj size,retains
R4747 T17443 T17435 prep until,retains
R4748 T17444 T17445 det the,age
R4749 T17445 T17443 pobj age,until
R4750 T17446 T17447 amod young,adult
R4751 T17447 T17445 nmod adult,age
R4752 T17448 T17435 cc and,retains
R4753 T17449 T17435 conj regresses,retains
R4754 T17450 T17449 advmod thereafter,regresses
R4755 T17451 T17449 prep by,regresses
R4756 T17452 T17451 pobj atrophy,by
R4757 T17453 T17435 punct .,retains
R4758 T17455 T17456 prep In,is
R4759 T17457 T17458 det the,mice
R4760 T17458 T17455 pobj mice,In
R4761 T17459 T17458 amod normal,mice
R4762 T17460 T17458 amod young,mice
R4763 T17461 T17462 nsubj we,examined
R4764 T17462 T17458 advcl examined,mice
R4765 T17463 T17464 punct (,P3
R4766 T17464 T17458 parataxis P3,mice
R4767 T17465 T17466 punct –,P17
R4768 T17466 T17464 prep P17,P3
R4769 T17467 T17464 punct ),P3
R4770 T17468 T17456 punct ", ",is
R4771 T17469 T17456 nsubj it,is
R4772 T17470 T17456 acomp evident,is
R4773 T17471 T17472 mark that,were
R4774 T17472 T17456 ccomp were,is
R4775 T17473 T17472 nsubj thymocytes,were
R4776 T17474 T17475 advmod mitotically,active
R4777 T17475 T17472 acomp active,were
R4778 T17476 T17472 prep in,were
R4779 T17477 T17478 det the,cortex
R4780 T17478 T17476 pobj cortex,in
R4781 T17479 T17480 mark as,determined
R4782 T17480 T17472 advcl determined,were
R4783 T17481 T17480 prep by,determined
R4784 T17482 T17483 compound BrdU,immunostaining
R4785 T17483 T17481 pobj immunostaining,by
R4786 T17484 T17485 punct (,6B
R4787 T17485 T17456 parataxis 6B,is
R4788 T17486 T17485 compound Figure,6B
R4789 T17487 T17485 punct ),6B
R4790 T17488 T17456 punct .,is
R4791 T17490 T17491 nsubj Immunohistochemistry,showed
R4792 T17492 T17490 prep of,Immunohistochemistry
R4793 T17493 T17494 amod normal,thymus
R4794 T17494 T17492 pobj thymus,of
R4795 T17495 T17494 prep from,thymus
R4796 T17496 T17497 nmod P3,mice
R4797 T17497 T17495 pobj mice,from
R4798 T17498 T17496 prep to,P3
R4799 T17499 T17498 pobj P17,to
R4800 T17500 T17501 det a,pattern
R4801 T17501 T17491 dobj pattern,showed
R4802 T17502 T17501 amod similar,pattern
R4803 T17503 T17501 compound staining,pattern
R4804 T17504 T17501 prep for,pattern
R4805 T17505 T17504 pobj K14,for
R4806 T17506 T17507 mark in,restricted
R4807 T17507 T17491 advcl restricted,showed
R4808 T17508 T17507 mark that,restricted
R4809 T17509 T17510 poss its,expression
R4810 T17510 T17507 nsubjpass expression,restricted
R4811 T17511 T17507 auxpass was,restricted
R4812 T17512 T17507 prep to,restricted
R4813 T17513 T17514 det a,population
R4814 T17514 T17512 pobj population,to
R4815 T17515 T17514 amod small,population
R4816 T17516 T17514 prep of,population
R4817 T17517 T17516 pobj TECs,of
R4818 T17518 T17514 prep in,population
R4819 T17519 T17520 det the,region
R4820 T17520 T17518 pobj region,in
R4821 T17521 T17520 amod inner,region
R4822 T17522 T17520 amod medullary,region
R4823 T17523 T17518 cc and,in
R4824 T17524 T17518 conj in,in
R4825 T17525 T17526 det the,keratinocytes
R4826 T17526 T17524 pobj keratinocytes,in
R4827 T17527 T17526 prep in,keratinocytes
R4828 T17528 T17529 poss Hassall,corpuscles
R4829 T17529 T17527 pobj corpuscles,in
R4830 T17530 T17528 case 's,Hassall
R4831 T17531 T17532 punct (,6D
R4832 T17532 T17491 parataxis 6D,showed
R4833 T17533 T17532 compound Figure,6D
R4834 T17534 T17532 punct ),6D
R4835 T17535 T17491 punct .,showed
R4836 T17537 T17538 amod Diffuse,staining
R4837 T17538 T17540 nsubjpass staining,detected
R4838 T17539 T17538 amod cytoplasmic,staining
R4839 T17541 T17538 prep for,staining
R4840 T17542 T17543 compound β,catenin
R4841 T17543 T17541 pobj catenin,for
R4842 T17544 T17543 punct -,catenin
R4843 T17545 T17540 auxpass was,detected
R4844 T17546 T17540 advmod also,detected
R4845 T17547 T17540 prep in,detected
R4846 T17548 T17549 det the,cells
R4847 T17549 T17547 pobj cells,in
R4848 T17550 T17549 amod medullary,cells
R4849 T17551 T17549 amod epithelial,cells
R4850 T17552 T17553 punct (,6C
R4851 T17553 T17540 parataxis 6C,detected
R4852 T17554 T17553 compound Figure,6C
R4853 T17555 T17553 punct ),6C
R4854 T17556 T17540 punct .,detected
R4855 T17558 T17559 prep In,observed
R4856 T17560 T17558 pobj contrast,In
R4857 T17561 T17560 prep to,contrast
R4858 T17562 T17563 compound K14,expression
R4859 T17563 T17561 pobj expression,to
R4860 T17564 T17559 punct ", ",observed
R4861 T17565 T17566 amod diffuse,staining
R4862 T17566 T17559 nsubjpass staining,observed
R4863 T17567 T17566 prep for,staining
R4864 T17568 T17567 pobj K8,for
R4865 T17569 T17559 auxpass was,observed
R4866 T17570 T17559 prep in,observed
R4867 T17571 T17572 amod epithelial,cells
R4868 T17572 T17570 pobj cells,in
R4869 T17573 T17574 preconj both,in
R4870 T17574 T17559 prep in,observed
R4871 T17575 T17576 det the,medulla
R4872 T17576 T17574 pobj medulla,in
R4873 T17577 T17576 cc and,medulla
R4874 T17578 T17576 conj cortex,medulla
R4875 T17579 T17580 punct (,S3
R4876 T17580 T17559 parataxis S3,observed
R4877 T17581 T17580 compound Figure,S3
R4878 T17582 T17580 punct ),S3
R4879 T17583 T17559 punct .,observed
R4880 T17585 T17586 compound K1,staining
R4881 T17586 T17587 nsubjpass staining,detected
R4882 T17588 T17587 auxpass was,detected
R4883 T17589 T17587 neg not,detected
R4884 T17590 T17587 prep in,detected
R4885 T17591 T17592 amod young,mice
R4886 T17592 T17590 pobj mice,in
R4887 T17593 T17587 prep at,detected
R4888 T17594 T17593 pobj P3,at
R4889 T17595 T17587 cc but,detected
R4890 T17596 T17597 prep in,detected
R4891 T17597 T17587 conj detected,detected
R4892 T17598 T17599 amod older,mice
R4893 T17599 T17596 pobj mice,in
R4894 T17600 T17597 nsubjpass it,detected
R4895 T17601 T17597 auxpass was,detected
R4896 T17602 T17597 prep in,detected
R4897 T17603 T17604 amod differentiated,keratinocytes
R4898 T17604 T17602 pobj keratinocytes,in
R4899 T17605 T17597 prep in,detected
R4900 T17606 T17605 pobj some,in
R4901 T17607 T17606 prep of,some
R4902 T17608 T17609 poss Hassall,corpuscles
R4903 T17609 T17607 pobj corpuscles,of
R4904 T17610 T17608 case 's,Hassall
R4905 T17611 T17612 punct (,S3
R4906 T17612 T17597 parataxis S3,detected
R4907 T17613 T17612 compound Figure,S3
R4908 T17614 T17612 punct ),S3
R4909 T17615 T17597 punct .,detected
R4910 T17617 T17618 det The,abnormalities
R4911 T17618 T17620 nsubj abnormalities,were
R4912 T17619 T17618 amod histological,abnormalities
R4913 T17621 T17618 prep of,abnormalities
R4914 T17622 T17621 pobj thymus,of
R4915 T17623 T17620 acomp evident,were
R4916 T17624 T17625 advmod as,early
R4917 T17625 T17620 advmod early,were
R4918 T17626 T17625 prep as,early
R4919 T17627 T17626 pobj P3,as
R4920 T17628 T17620 prep in,were
R4921 T17629 T17630 compound KA,mutants
R4922 T17630 T17628 pobj mutants,in
R4923 T17631 T17632 punct (,6E
R4924 T17632 T17620 parataxis 6E,were
R4925 T17633 T17632 compound Figure,6E
R4926 T17634 T17632 cc and,6E
R4927 T17635 T17632 conj 6H,6E
R4928 T17636 T17632 punct ),6E
R4929 T17637 T17620 punct .,were
R4930 T17639 T17640 det The,thymus
R4931 T17640 T17641 nsubjpass thymus,made
R4932 T17642 T17641 auxpass was,made
R4933 T17643 T17641 prep of,made
R4934 T17644 T17645 nummod two,lobules
R4935 T17645 T17643 pobj lobules,of
R4936 T17646 T17641 prep as,made
R4937 T17647 T17646 prep in,as
R4938 T17648 T17649 det the,mice
R4939 T17649 T17647 pobj mice,in
R4940 T17650 T17649 amod normal,mice
R4941 T17651 T17641 cc but,made
R4942 T17652 T17653 det the,thymus
R4943 T17653 T17655 nsubj thymus,was
R4944 T17654 T17653 amod mutant,thymus
R4945 T17655 T17641 conj was,made
R4946 T17656 T17657 advmod significantly,smaller
R4947 T17657 T17655 acomp smaller,was
R4948 T17658 T17657 prep in,smaller
R4949 T17659 T17658 pobj size,in
R4950 T17660 T17657 prep than,smaller
R4951 T17661 T17660 pobj that,than
R4952 T17662 T17661 prep of,that
R4953 T17663 T17664 det the,controls
R4954 T17664 T17662 pobj controls,of
R4955 T17665 T17666 npadvmod age,matched
R4956 T17666 T17664 amod matched,controls
R4957 T17667 T17666 punct -,matched
R4958 T17668 T17669 punct (,2G
R4959 T17669 T17655 parataxis 2G,was
R4960 T17670 T17669 compound Figure,2G
R4961 T17671 T17669 punct ),2G
R4962 T17672 T17655 punct .,was
R4963 T17674 T17675 advmod Interestingly,reflected
R4964 T17676 T17675 punct ", ",reflected
R4965 T17677 T17675 nsubjpass variations,reflected
R4966 T17678 T17677 prep in,variations
R4967 T17679 T17680 det the,severity
R4968 T17680 T17678 pobj severity,in
R4969 T17681 T17680 amod phenotypic,severity
R4970 T17682 T17680 prep of,severity
R4971 T17683 T17684 det the,pups
R4972 T17684 T17682 pobj pups,of
R4973 T17685 T17684 amod mutant,pups
R4974 T17686 T17677 prep at,variations
R4975 T17687 T17686 pobj P3,at
R4976 T17688 T17675 auxpass were,reflected
R4977 T17689 T17675 advmod prominently,reflected
R4978 T17690 T17675 prep in,reflected
R4979 T17691 T17692 det the,extent
R4980 T17692 T17690 pobj extent,in
R4981 T17693 T17692 prep of,extent
R4982 T17694 T17695 amod histological,abnormalities
R4983 T17695 T17693 pobj abnormalities,of
R4984 T17696 T17695 prep of,abnormalities
R4985 T17697 T17696 pobj thymus,of
R4986 T17698 T17675 punct .,reflected
R4987 T17700 T17701 det A,pup
R4988 T17701 T17705 nsubj pup,showed
R4989 T17702 T17701 nmod P3,pup
R4990 T17703 T17701 nmod KA,pup
R4991 T17704 T17701 amod mutant,pup
R4992 T17706 T17707 dep that,showed
R4993 T17707 T17701 relcl showed,pup
R4994 T17708 T17709 amod milder,phenotype
R4995 T17709 T17707 dobj phenotype,showed
R4996 T17710 T17709 prep with,phenotype
R4997 T17711 T17712 det a,weight
R4998 T17712 T17710 pobj weight,with
R4999 T17713 T17712 amod comparable,weight
R5000 T17714 T17712 compound body,weight
R5001 T17715 T17712 prep to,weight
R5002 T17716 T17717 poss its,littermates
R5003 T17717 T17715 pobj littermates,to
R5004 T17718 T17717 amod normal,littermates
R5005 T17719 T17720 punct (,2A
R5006 T17720 T17707 parataxis 2A,showed
R5007 T17721 T17720 compound Figure,2A
R5008 T17722 T17720 punct ", ",2A
R5009 T17723 T17720 npadvmod M2,2A
R5010 T17724 T17720 punct ),2A
R5011 T17725 T17726 amod milder,abnormalities
R5012 T17726 T17705 dobj abnormalities,showed
R5013 T17727 T17726 compound thymus,abnormalities
R5014 T17728 T17729 punct (,6E
R5015 T17729 T17726 parataxis 6E,abnormalities
R5016 T17730 T17729 compound Figure,6E
R5017 T17731 T17729 punct ),6E
R5018 T17732 T17705 prep compared,showed
R5019 T17733 T17732 prep to,compared
R5020 T17734 T17735 poss its,littermate
R5021 T17735 T17733 pobj littermate,to
R5022 T17736 T17737 advmod more,severe
R5023 T17737 T17735 amod severe,littermate
R5024 T17738 T17735 amod mutant,littermate
R5025 T17739 T17740 punct (,2A
R5026 T17740 T17705 parataxis 2A,showed
R5027 T17741 T17740 compound Figure,2A
R5028 T17742 T17740 punct ", ",2A
R5029 T17743 T17740 npadvmod M1,2A
R5030 T17744 T17740 punct ;,2A
R5031 T17745 T17746 compound Figure,6H
R5032 T17746 T17740 appos 6H,2A
R5033 T17747 T17740 punct ),2A
R5034 T17748 T17705 punct .,showed
R5035 T17750 T17751 det The,thymus
R5036 T17751 T17755 nsubj thymus,was
R5037 T17752 T17751 amod milder,thymus
R5038 T17753 T17751 nmod P3,thymus
R5039 T17754 T17751 amod mutant,thymus
R5040 T17756 T17755 advmod already,was
R5041 T17757 T17758 advmod much,smaller
R5042 T17758 T17755 acomp smaller,was
R5043 T17759 T17758 prep in,smaller
R5044 T17760 T17759 pobj size,in
R5045 T17761 T17755 prep compared,was
R5046 T17762 T17761 prep to,compared
R5047 T17763 T17762 pobj those,to
R5048 T17764 T17763 prep of,those
R5049 T17765 T17766 amod normal,littermates
R5050 T17766 T17764 pobj littermates,of
R5051 T17767 T17768 punct (,shown
R5052 T17768 T17755 parataxis shown,was
R5053 T17769 T17768 nsubj data,shown
R5054 T17770 T17768 neg not,shown
R5055 T17771 T17768 punct ),shown
R5056 T17772 T17755 cc but,was
R5057 T17773 T17774 nummod two,compartments
R5058 T17774 T17776 nsubj compartments,were
R5059 T17775 T17774 amod epithelial,compartments
R5060 T17776 T17755 conj were,was
R5061 T17777 T17774 prep of,compartments
R5062 T17778 T17777 pobj thymus,of
R5063 T17779 T17776 advmod histologically,were
R5064 T17780 T17776 advmod still,were
R5065 T17781 T17776 acomp distinguishable,were
R5066 T17782 T17776 punct ", ",were
R5067 T17783 T17784 mark with,evident
R5068 T17784 T17776 advcl evident,were
R5069 T17785 T17784 nsubj colonization,evident
R5070 T17786 T17785 prep of,colonization
R5071 T17787 T17786 pobj thymocytes,of
R5072 T17788 T17784 prep in,evident
R5073 T17789 T17790 det the,cortex
R5074 T17790 T17788 pobj cortex,in
R5075 T17791 T17776 punct .,were
R5076 T17793 T17794 advmod However,were
R5077 T17795 T17794 punct ", ",were
R5078 T17796 T17794 expl there,were
R5079 T17797 T17798 amod small,populations
R5080 T17798 T17794 attr populations,were
R5081 T17799 T17798 prep of,populations
R5082 T17800 T17801 advmod lightly,stained
R5083 T17801 T17802 amod stained,cells
R5084 T17802 T17799 pobj cells,of
R5085 T17803 T17798 prep by,populations
R5086 T17804 T17803 pobj H,by
R5087 T17805 T17804 cc &,H
R5088 T17806 T17804 conj E,H
R5089 T17807 T17798 acl extending,populations
R5090 T17808 T17807 prep from,extending
R5091 T17809 T17810 det the,edge
R5092 T17810 T17808 pobj edge,from
R5093 T17811 T17810 prep of,edge
R5094 T17812 T17813 det the,cortex
R5095 T17813 T17811 pobj cortex,of
R5096 T17814 T17813 amod outer,cortex
R5097 T17815 T17807 prep towards,extending
R5098 T17816 T17817 amod inner,medulla
R5099 T17817 T17815 pobj medulla,towards
R5100 T17818 T17819 punct (,6E
R5101 T17819 T17794 parataxis 6E,were
R5102 T17820 T17819 compound Figure,6E
R5103 T17821 T17819 punct ),6E
R5104 T17822 T17794 punct ", ",were
R5105 T17823 T17794 cc and,were
R5106 T17824 T17825 det these,cells
R5107 T17825 T17826 nsubj cells,showed
R5108 T17826 T17794 conj showed,were
R5109 T17827 T17828 amod intense,staining
R5110 T17828 T17826 dobj staining,showed
R5111 T17829 T17828 amod nuclear,staining
R5112 T17830 T17831 compound β,catenin
R5113 T17831 T17828 compound catenin,staining
R5114 T17832 T17831 punct -,catenin
R5115 T17833 T17834 mark whereas,showed
R5116 T17834 T17826 advcl showed,showed
R5117 T17835 T17836 det the,rest
R5118 T17836 T17834 nsubj rest,showed
R5119 T17837 T17836 prep of,rest
R5120 T17838 T17839 det the,cells
R5121 T17839 T17837 pobj cells,of
R5122 T17840 T17839 amod medullary,cells
R5123 T17841 T17842 amod diffuse,pattern
R5124 T17842 T17834 dobj pattern,showed
R5125 T17843 T17844 compound β,catenin
R5126 T17844 T17842 compound catenin,pattern
R5127 T17845 T17844 punct -,catenin
R5128 T17846 T17842 compound staining,pattern
R5129 T17847 T17842 amod similar,pattern
R5130 T17848 T17847 prep to,similar
R5131 T17849 T17848 pobj that,to
R5132 T17850 T17849 prep of,that
R5133 T17851 T17852 det the,control
R5134 T17852 T17850 pobj control,of
R5135 T17853 T17854 punct (,6F
R5136 T17854 T17826 parataxis 6F,showed
R5137 T17855 T17854 compound Figure,6F
R5138 T17856 T17854 punct ),6F
R5139 T17857 T17826 punct .,showed
R5140 T17859 T17860 nsubjpass Localization,limited
R5141 T17861 T17859 prep of,Localization
R5142 T17862 T17861 pobj K14,of
R5143 T17863 T17860 auxpass was,limited
R5144 T17864 T17860 prep to,limited
R5145 T17865 T17866 det a,cells
R5146 T17866 T17864 pobj cells,to
R5147 T17867 T17866 amod few,cells
R5148 T17868 T17866 prep in,cells
R5149 T17869 T17870 det the,medulla
R5150 T17870 T17868 pobj medulla,in
R5151 T17871 T17860 cc and,limited
R5152 T17872 T17873 nsubj some,overlapped
R5153 T17873 T17860 conj overlapped,limited
R5154 T17874 T17873 prep with,overlapped
R5155 T17875 T17876 compound K8,localization
R5156 T17876 T17874 pobj localization,with
R5157 T17877 T17878 punct (,6G
R5158 T17878 T17873 parataxis 6G,overlapped
R5159 T17879 T17878 compound Figure,6G
R5160 T17880 T17878 punct ),6G
R5161 T17881 T17873 punct .,overlapped
R5162 T17883 T17884 prep In,lost
R5163 T17885 T17886 det the,thymus
R5164 T17886 T17883 pobj thymus,In
R5165 T17887 T17886 amod other,thymus
R5166 T17888 T17886 nmod P3,thymus
R5167 T17889 T17886 amod mutant,thymus
R5168 T17890 T17891 det the,compartments
R5169 T17891 T17884 nsubjpass compartments,lost
R5170 T17892 T17891 amod distinct,compartments
R5171 T17893 T17894 amod thymic,epithelial
R5172 T17894 T17891 amod epithelial,compartments
R5173 T17895 T17884 aux have,lost
R5174 T17896 T17884 auxpass been,lost
R5175 T17897 T17884 advmod completely,lost
R5176 T17898 T17884 punct ", ",lost
R5177 T17899 T17884 cc and,lost
R5178 T17900 T17901 advmod only,lymphocytes
R5179 T17901 T17904 nsubj lymphocytes,remaining
R5180 T17902 T17901 det a,lymphocytes
R5181 T17903 T17901 amod few,lymphocytes
R5182 T17904 T17884 conj remaining,lost
R5183 T17905 T17904 aux were,remaining
R5184 T17906 T17904 prep at,remaining
R5185 T17907 T17908 det the,edges
R5186 T17908 T17906 pobj edges,at
R5187 T17909 T17904 cc and,remaining
R5188 T17910 T17904 conj some,remaining
R5189 T17911 T17910 prep in,some
R5190 T17912 T17913 det the,middle
R5191 T17913 T17911 pobj middle,in
R5192 T17914 T17915 punct (,6H
R5193 T17915 T17910 parataxis 6H,some
R5194 T17916 T17915 compound Figure,6H
R5195 T17917 T17915 punct ),6H
R5196 T17918 T17904 punct .,remaining
R5197 T17920 T17921 amod Proliferative,activities
R5198 T17921 T17922 nsubjpass activities,observed
R5199 T17923 T17922 auxpass were,observed
R5200 T17924 T17925 neg no,longer
R5201 T17925 T17922 advmod longer,observed
R5202 T17926 T17922 prep in,observed
R5203 T17927 T17926 pobj thymocytes,in
R5204 T17928 T17929 advmod as,prominently
R5205 T17929 T17922 advmod prominently,observed
R5206 T17930 T17929 prep as,prominently
R5207 T17931 T17930 prep in,as
R5208 T17932 T17933 det the,thymus
R5209 T17933 T17931 pobj thymus,in
R5210 T17934 T17933 amod normal,thymus
R5211 T17935 T17922 punct ", ",observed
R5212 T17936 T17922 cc but,observed
R5213 T17937 T17938 det the,cells
R5214 T17938 T17940 nsubj cells,seemed
R5215 T17939 T17938 amod epithelial,cells
R5216 T17940 T17922 conj seemed,observed
R5217 T17941 T17942 aux to,forming
R5218 T17942 T17940 xcomp forming,seemed
R5219 T17943 T17942 aux be,forming
R5220 T17944 T17945 amod concentric,structures
R5221 T17945 T17942 dobj structures,forming
R5222 T17946 T17947 punct (,6I
R5223 T17947 T17942 parataxis 6I,forming
R5224 T17948 T17947 compound Figure,6I
R5225 T17949 T17947 punct ),6I
R5226 T17950 T17940 punct .,seemed
R5227 T17952 T17953 prep Unlike,showed
R5228 T17954 T17952 prep in,Unlike
R5229 T17955 T17956 det the,thymi
R5230 T17956 T17954 pobj thymi,in
R5231 T17957 T17956 amod normal,thymi
R5232 T17958 T17957 cc or,normal
R5233 T17959 T17957 conj mild,normal
R5234 T17960 T17956 amod mutant,thymi
R5235 T17961 T17953 punct ", ",showed
R5236 T17962 T17963 det the,thymus
R5237 T17963 T17953 nsubj thymus,showed
R5238 T17964 T17963 amod severe,thymus
R5239 T17965 T17963 nmod P3,thymus
R5240 T17966 T17963 amod mutant,thymus
R5241 T17967 T17968 amod extensive,expression
R5242 T17968 T17953 dobj expression,showed
R5243 T17969 T17968 compound K14,expression
R5244 T17970 T17971 dep that,overlapped
R5245 T17971 T17968 relcl overlapped,expression
R5246 T17972 T17971 prep with,overlapped
R5247 T17973 T17974 compound K8,expression
R5248 T17974 T17972 pobj expression,with
R5249 T17975 T17976 punct (,6K
R5250 T17976 T17953 parataxis 6K,showed
R5251 T17977 T17976 compound Figure,6K
R5252 T17978 T17976 punct ),6K
R5253 T17979 T17953 punct .,showed
R5254 T17981 T17982 det These,cells
R5255 T17982 T17983 nsubj cells,were
R5256 T17984 T17985 advmod more,like
R5257 T17985 T17983 prep like,were
R5258 T17986 T17987 amod basal,cells
R5259 T17987 T17985 pobj cells,like
R5260 T17988 T17987 prep of,cells
R5261 T17989 T17990 det the,skin
R5262 T17990 T17988 pobj skin,of
R5263 T17991 T17983 prep than,were
R5264 T17992 T17991 pobj TECs,than
R5265 T17993 T17983 cc and,were
R5266 T17994 T17983 conj were,were
R5267 T17995 T17994 acomp adjacent,were
R5268 T17996 T17995 prep to,adjacent
R5269 T17997 T17998 det the,cells
R5270 T17998 T17996 pobj cells,to
R5271 T17999 T18000 advmod most,immature
R5272 T18000 T17998 amod immature,cells
R5273 T18001 T17998 amod looking,cells
R5274 T18002 T18003 dep that,showing
R5275 T18003 T17998 relcl showing,cells
R5276 T18004 T18003 aux were,showing
R5277 T18005 T18006 amod strong,staining
R5278 T18006 T18003 dobj staining,showing
R5279 T18007 T18006 amod nuclear,staining
R5280 T18008 T18007 cc and,nuclear
R5281 T18009 T18007 conj cytoplasmic,nuclear
R5282 T18010 T18011 compound β,catenin
R5283 T18011 T18006 compound catenin,staining
R5284 T18012 T18011 punct -,catenin
R5285 T18013 T18014 punct (,6J
R5286 T18014 T17994 parataxis 6J,were
R5287 T18015 T18014 compound Figure,6J
R5288 T18016 T18014 punct ),6J
R5289 T18017 T17983 punct .,were
R5290 T18019 T18020 det The,staining
R5291 T18020 T18022 nsubjpass staining,observed
R5292 T18021 T18020 amod nuclear,staining
R5293 T18023 T18020 prep of,staining
R5294 T18024 T18025 compound β,catenin
R5295 T18025 T18023 pobj catenin,of
R5296 T18026 T18025 punct -,catenin
R5297 T18027 T18022 auxpass was,observed
R5298 T18028 T18022 neg not,observed
R5299 T18029 T18022 prep in,observed
R5300 T18030 T18031 det the,thymus
R5301 T18031 T18029 pobj thymus,in
R5302 T18032 T18031 amod normal,thymus
R5303 T18033 T18034 npadvmod age,matched
R5304 T18034 T18031 amod matched,thymus
R5305 T18035 T18034 punct -,matched
R5306 T18036 T18037 punct (,6C
R5307 T18037 T18022 parataxis 6C,observed
R5308 T18038 T18037 compound Figure,6C
R5309 T18039 T18037 punct ),6C
R5310 T18040 T18022 punct .,observed
R5311 T18042 T18043 advmod Most,notably
R5312 T18043 T18044 advmod notably,were
R5313 T18045 T18044 punct ", ",were
R5314 T18046 T18047 det the,patterns
R5315 T18047 T18044 nsubj patterns,were
R5316 T18048 T18047 nmod K14,patterns
R5317 T18049 T18048 cc and,K14
R5318 T18050 T18051 compound β,catenin
R5319 T18051 T18048 conj catenin,K14
R5320 T18052 T18051 punct -,catenin
R5321 T18053 T18047 compound staining,patterns
R5322 T18054 T18055 advmod mutually,exclusive
R5323 T18055 T18044 acomp exclusive,were
R5324 T18056 T18057 punct (,6J
R5325 T18057 T18044 parataxis 6J,were
R5326 T18058 T18057 compound Figure,6J
R5327 T18059 T18057 cc and,6J
R5328 T18060 T18057 conj 6K,6J
R5329 T18061 T18057 punct ),6J
R5330 T18062 T18044 punct .,were
R5331 T18064 T18065 prep At,consisted
R5332 T18066 T18064 pobj P10,At
R5333 T18067 T18068 punct –,P13
R5334 T18068 T18066 prep P13,P10
R5335 T18069 T18065 punct ", ",consisted
R5336 T18070 T18071 det the,thymus
R5337 T18071 T18065 nsubj thymus,consisted
R5338 T18072 T18071 amod mutant,thymus
R5339 T18073 T18065 prep of,consisted
R5340 T18074 T18075 amod numerous,structures
R5341 T18075 T18073 pobj structures,of
R5342 T18076 T18075 amod enlarged,structures
R5343 T18077 T18075 poss Hassall,structures
R5344 T18078 T18077 case 's,Hassall
R5345 T18079 T18080 npadvmod corpuscle,like
R5346 T18080 T18075 amod like,structures
R5347 T18081 T18080 punct –,like
R5348 T18082 T18075 punct ", ",structures
R5349 T18083 T18075 acl made,structures
R5350 T18084 T18083 prep of,made
R5351 T18085 T18084 pobj arrays,of
R5352 T18086 T18085 prep of,arrays
R5353 T18087 T18088 npadvmod K14,expressing
R5354 T18088 T18093 amod expressing,cells
R5355 T18089 T18087 punct -,K14
R5356 T18090 T18087 cc and,K14
R5357 T18137 T18138 npadvmod differentiation,specific
R5358 T18091 T18087 conj K8,K14
R5359 T18138 T18140 amod specific,markers
R5360 T18092 T18088 punct -,expressing
R5361 T18139 T18138 punct -,specific
R5362 T18140 T18136 pobj markers,of
R5363 T18093 T18086 pobj cells,of
R5364 T18141 T18140 prep depending,markers
R5365 T18142 T18141 prep on,depending
R5366 T18143 T18144 det the,age
R5367 T18094 T18093 amod keratinizing,cells
R5368 T18144 T18142 pobj age,on
R5369 T18145 T18144 prep of,age
R5370 T18095 T18093 amod epithelial,cells
R5371 T18146 T18145 pobj mice,of
R5372 T18147 T18140 punct ", ",markers
R5373 T18148 T18149 prep in,K1
R5374 T18096 T18093 acl surrounding,cells
R5375 T18149 T18140 appos K1,markers
R5376 T18150 T18151 det this,case
R5377 T18151 T18148 pobj case,in
R5378 T18097 T18098 amod large,deposits
R5379 T18098 T18096 dobj deposits,surrounding
R5380 T18152 T18149 cc and,K1
R5381 T18153 T18149 conj involucrin,K1
R5382 T18154 T18155 dep that,are
R5383 T18155 T18149 relcl are,K1
R5384 T18156 T18155 advmod normally,are
R5385 T18099 T18098 compound keratin,deposits
R5386 T18157 T18155 acomp present,are
R5387 T18158 T18159 advmod only,in
R5388 T18159 T18155 prep in,are
R5389 T18160 T18161 poss Hassall,corpuscles
R5390 T18100 T18101 punct (,6L
R5391 T18161 T18159 pobj corpuscles,in
R5392 T18162 T18160 case 's,Hassall
R5393 T18101 T18065 parataxis 6L,consisted
R5394 T18163 T18135 punct ", ",detected
R5395 T18164 T18135 auxpass were,detected
R5396 T18165 T18135 advmod also,detected
R5397 T18102 T18101 compound Figure,6L
R5398 T18166 T18135 prep in,detected
R5399 T18103 T18101 cc and,6L
R5400 T18167 T18168 amod mutant,thymi
R5401 T18168 T18166 pobj thymi,in
R5402 T18169 T18170 punct (,S3
R5403 T18170 T18135 parataxis S3,detected
R5404 T18171 T18170 compound Figure,S3
R5405 T18104 T18101 conj 6O,6L
R5406 T18172 T18170 punct ),S3
R5407 T18173 T18135 punct .,detected
R5408 T18105 T18101 punct ),6L
R5409 T18175 T18176 prep In,were
R5410 T18106 T18065 punct .,consisted
R5411 T18177 T18178 det these,mice
R5412 T18178 T18175 pobj mice,In
R5413 T18179 T18180 det no,thymocytes
R5414 T18108 T18109 expl There,were
R5415 T18180 T18176 nsubj thymocytes,were
R5416 T18181 T18176 acomp detectable,were
R5417 T18182 T18176 punct .,were
R5418 T18109 T18110 ccomp were,called
R5419 T18184 T18185 compound BrdU,incorporation
R5420 T18185 T18186 nsubjpass incorporation,looking
R5421 T18111 T18112 amod numerous,neutrophils
R5422 T18187 T18186 auxpass was,looking
R5423 T18188 T18186 advmod only,looking
R5424 T18189 T18186 aux observed,looking
R5425 T18190 T18186 prep in,looking
R5426 T18112 T18109 attr neutrophils,were
R5427 T18191 T18192 advmod very,few
R5428 T18192 T18193 amod few,cells
R5429 T18113 T18112 cc and,neutrophils
R5430 T18193 T18190 pobj cells,in
R5431 T18194 T18193 amod keratinizing,cells
R5432 T18195 T18193 amod epithelial,cells
R5433 T18114 T18112 conj macrophages,neutrophils
R5434 T18196 T18186 punct ", ",looking
R5435 T18197 T18198 advmod somewhat,similar
R5436 T18198 T18186 acomp similar,looking
R5437 T18199 T18198 prep to,similar
R5438 T18200 T18201 det the,pattern
R5439 T18201 T18199 pobj pattern,to
R5440 T18115 T18112 acl infiltrating,neutrophils
R5441 T18202 T18201 prep of,pattern
R5442 T18203 T18204 amod mature,skin
R5443 T18204 T18202 pobj skin,of
R5444 T18116 T18117 det the,thymus
R5445 T18205 T18206 punct (,6M
R5446 T18206 T18186 parataxis 6M,looking
R5447 T18207 T18206 compound Figure,6M
R5448 T18208 T18206 punct ),6M
R5449 T18117 T18115 dobj thymus,infiltrating
R5450 T18209 T18186 punct .,looking
R5451 T18118 T18115 prep in,infiltrating
R5452 T18211 T18212 det The,expression
R5453 T18212 T18214 nsubj expression,was
R5454 T18213 T18212 amod diffuse,expression
R5455 T18119 T18118 pobj response,in
R5456 T18215 T18212 prep of,expression
R5457 T18120 T18119 prep to,response
R5458 T18216 T18217 compound β,catenin
R5459 T18217 T18215 pobj catenin,of
R5460 T18218 T18217 punct -,catenin
R5461 T18121 T18122 det these,keratins
R5462 T18219 T18214 advmod also,was
R5463 T18220 T18214 acomp present,was
R5464 T18221 T18214 prep in,was
R5465 T18122 T18120 pobj keratins,to
R5466 T18222 T18223 det these,cells
R5467 T18223 T18221 pobj cells,in
R5468 T18224 T18223 amod epithelial,cells
R5469 T18123 T18110 punct ;,called
R5470 T18225 T18214 punct ", ",was
R5471 T18226 T18214 cc and,was
R5472 T18227 T18228 prep at,were
R5473 T18124 T18110 advmod hence,called
R5474 T18228 T18214 conj were,was
R5475 T18229 T18230 det this,age
R5476 T18230 T18227 pobj age,at
R5477 T18231 T18232 amod fewer,cells
R5478 T18125 T18110 punct ", ",called
R5479 T18232 T18228 nsubj cells,were
R5480 T18233 T18228 acomp positive,were
R5481 T18126 T18127 det these,structures
R5482 T18234 T18233 prep for,positive
R5483 T18235 T18236 amod nuclear,staining
R5484 T18127 T18110 nsubjpass structures,called
R5485 T18236 T18234 pobj staining,for
R5486 T18237 T18238 compound β,catenin
R5487 T18238 T18236 compound catenin,staining
R5488 T18239 T18238 punct -,catenin
R5489 T18128 T18110 aux could,called
R5490 T18240 T18241 punct (,6N
R5491 T18241 T18228 parataxis 6N,were
R5492 T18242 T18241 compound Figure,6N
R5493 T18129 T18110 auxpass be,called
R5494 T18130 T18110 oprd pyogranuloma,called
R5495 T18131 T18110 punct .,called
R5496 T18133 T18134 amod Varying,degrees
R5497 T18243 T18241 punct ),6N
R5498 T18134 T18135 nsubjpass degrees,detected
R5499 T18244 T18228 punct .,were
R5500 T18246 T18247 prep As,observed
R5501 T18136 T18134 prep of,degrees
R5502 T18248 T18246 prep in,As
R5503 T18249 T18250 det the,mice
R5504 T18349 T18346 cc and,loss
R5505 T18250 T18248 pobj mice,in
R5506 T18251 T18250 amod younger,mice
R5507 T18252 T18250 amod mutant,mice
R5508 T18253 T18247 punct ", ",observed
R5509 T18350 T18351 amod consequent,stabilization
R5510 T18254 T18247 advmod however,observed
R5511 T18255 T18247 punct ", ",observed
R5512 T18351 T18346 conj stabilization,loss
R5513 T18256 T18257 amod nuclear,localization
R5514 T18257 T18247 nsubjpass localization,observed
R5515 T18258 T18257 prep of,localization
R5516 T18352 T18351 prep of,stabilization
R5517 T18259 T18260 compound β,catenin
R5518 T18260 T18258 pobj catenin,of
R5519 T18261 T18260 punct -,catenin
R5520 T18353 T18354 compound β,catenin
R5521 T18262 T18247 auxpass was,observed
R5522 T18263 T18247 advmod only,observed
R5523 T18264 T18247 prep in,observed
R5524 T18354 T18352 pobj catenin,of
R5525 T18265 T18266 npadvmod K14,negative
R5526 T18266 T18268 amod negative,cells
R5527 T18267 T18266 punct -,negative
R5528 T18268 T18264 pobj cells,in
R5529 T18355 T18354 punct -,catenin
R5530 T18269 T18270 dep that,looked
R5531 T18270 T18268 relcl looked,cells
R5532 T18356 T18346 prep in,loss
R5533 T18271 T18270 prep like,looked
R5534 T18272 T18273 amod undifferentiated,cells
R5535 T18273 T18271 pobj cells,like
R5536 T18357 T18358 npadvmod K14,expressing
R5537 T18274 T18273 amod basal,cells
R5538 T18275 T18247 punct .,observed
R5539 T18277 T18278 prep In,was
R5540 T18279 T18280 amod older,mice
R5541 T18358 T18360 amod expressing,TECs
R5542 T18280 T18277 pobj mice,In
R5543 T18281 T18280 compound P17,mice
R5544 T18282 T18278 punct ", ",was
R5545 T18359 T18358 punct -,expressing
R5546 T18283 T18284 det the,histopathology
R5547 T18284 T18278 nsubj histopathology,was
R5548 T18285 T18284 cc and,histopathology
R5549 T18360 T18356 pobj TECs,in
R5550 T18286 T18287 compound keratin,pattern
R5551 T18287 T18284 conj pattern,histopathology
R5552 T18361 T18345 prep to,lead
R5553 T18288 T18287 compound expression,pattern
R5554 T18289 T18284 prep of,histopathology
R5555 T18290 T18291 det the,thymus
R5556 T18362 T18363 poss their,proliferation
R5557 T18291 T18289 pobj thymus,of
R5558 T18292 T18291 amod mutant,thymus
R5559 T18293 T18278 acomp similar,was
R5560 T18363 T18361 pobj proliferation,to
R5561 T18294 T18293 prep to,similar
R5562 T18295 T18294 pobj that,to
R5563 T18296 T18295 prep of,that
R5564 T18364 T18363 amod aberrant,proliferation
R5565 T18297 T18296 pobj P13,of
R5566 T18298 T18278 prep except,was
R5567 T18365 T18363 cc and,proliferation
R5568 T18299 T18298 prep for,except
R5569 T18300 T18301 det the,fact
R5570 T18301 T18299 pobj fact,for
R5571 T18302 T18303 mark that,became
R5572 T18366 T18363 conj differentiation,proliferation
R5573 T18303 T18301 acl became,fact
R5574 T18304 T18305 compound β,catenin
R5575 T18367 T18366 prep to,differentiation
R5576 T18305 T18307 compound catenin,expression
R5577 T18306 T18305 punct -,catenin
R5578 T18307 T18303 nsubj expression,became
R5579 T18368 T18367 pobj keratinocytes,to
R5580 T18308 T18309 advmod increasingly,diffuse
R5581 T18309 T18303 acomp diffuse,became
R5582 T18310 T18303 cc and,became
R5583 T18311 T18303 conj appeared,became
R5584 T18369 T18345 punct ", ",lead
R5585 T18312 T18313 aux to,colocalize
R5586 T18313 T18311 xcomp colocalize,appeared
R5587 T18370 T18345 advcl causing,lead
R5588 T18314 T18313 prep with,colocalize
R5589 T18315 T18316 compound K8,K14
R5590 T18316 T18318 compound K14,expression
R5591 T18317 T18316 punct /,K14
R5592 T18318 T18314 pobj expression,with
R5593 T18319 T18320 punct (,shown
R5594 T18371 T18372 amod massive,metaplasia
R5595 T18320 T18278 parataxis shown,was
R5596 T18321 T18320 nsubj data,shown
R5597 T18322 T18320 neg not,shown
R5598 T18372 T18370 dobj metaplasia,causing
R5599 T18373 T18372 amod squamous,metaplasia
R5600 T18323 T18320 punct ),shown
R5601 T18374 T18370 punct ", ",causing
R5602 T18324 T18278 punct .,was
R5603 T18375 T18370 cc rather,causing
R5604 T18326 T18327 nsubj This,coincided
R5605 T18376 T18375 dep than,rather
R5606 T18328 T18327 prep with,coincided
R5607 T18329 T18330 amod fewer,cells
R5608 T18330 T18328 pobj cells,with
R5609 T18377 T18378 aux to,form
R5610 T18331 T18330 amod immature,cells
R5611 T18332 T18330 prep in,cells
R5612 T18378 T18370 conj form,causing
R5613 T18333 T18334 det the,thymus
R5614 T18334 T18332 pobj thymus,in
R5615 T18379 T18380 preconj either,medullary
R5616 T18335 T18334 amod older,thymus
R5617 T18336 T18334 amod mutant,thymus
R5618 T18337 T18327 punct .,coincided
R5619 T18380 T18381 amod medullary,TECs
R5620 T18339 T18340 advmod Collectively,suggest
R5621 T18381 T18378 dobj TECs,form
R5622 T18341 T18340 punct ", ",suggest
R5623 T18342 T18343 det these,results
R5624 T18382 T18380 cc or,medullary
R5625 T18343 T18340 nsubj results,suggest
R5626 T18344 T18345 mark that,lead
R5627 T18383 T18380 conj cortical,medullary
R5628 T18345 T18340 ccomp lead,suggest
R5629 T18346 T18345 nsubj loss,lead
R5630 T18347 T18346 prep of,loss
R5631 T18384 T18340 punct .,suggest
R5632 T18348 T18347 pobj Apc,of
R5633 T18386 T18387 nsubj Loss,resulted
R5634 T18388 T18386 prep of,Loss
R5635 T18389 T18390 amod proper,compartments
R5636 T18390 T18388 pobj compartments,of
R5637 T18391 T18390 compound TEC,compartments
R5638 T18392 T18387 advmod consequently,resulted
R5639 T18393 T18387 prep in,resulted
R5640 T18394 T18393 pobj loss,in
R5641 T18395 T18394 prep of,loss
R5642 T18396 T18395 pobj thymocytes,of
R5643 T18397 T18396 prep for,thymocytes
R5644 T18398 T18397 pobj maturation,for
R5645 T18399 T18394 cc and,loss
R5646 T18400 T18401 det the,mice
R5647 T18401 T18402 nsubj mice,be
R5648 T18402 T18394 conj be,loss
R5649 T18403 T18402 aux to,be
R5650 T18404 T18405 punct “,athymic
R5651 T18405 T18402 acomp athymic,be
R5652 T18406 T18387 punct .,resulted
R5653 T18407 T18387 punct ”,resulted
R5654 T19064 T19065 nsubjpass "Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus Role of APC in Skin and Its Appendages Abstract The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre–mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; ApcCKO/CKO mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial–mesenchymal interactions for their development. Synopsis Patients with familial adenomatous polyposis (FAP) and its variant, Gardner's syndrome, will develop hundreds of colorectal polyps. It is a heritable disease that is linked to a genetic mutation in the tumor suppressor gene APC (adenomatous polyposis coli). These individuals also develop extracolonic symptoms, among which are congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, epidermoid cysts, disorders of the maxillary and skeletal bones, and dental abnormalities, suggesting the importance of APC functions in these organs. To understand the role of Apc in development and in organs other than intestine, we generated Apc mutant mice that can conditionally delete the gene when exposed to Cre recombinase. These mice were mated with K14 (Keratin 14)–cre mice that express Cre recombinase in skin and its appendages. The authors found that the mutant mice that have lost Apc in K14-cre transgene–expressing tissues were viable, but had stunted growth and died before weaning. These mutant mice showed developmental abnormalities not only in skin but also in many epithelial-derived tissues, including teeth and thymus. This work demonstrates the importance of Apc in development of many organs, and provides new insights into diagnosis and management of patients with APC mutations. Introduction Adenomatous polyposis coli (APC) is a member of the Wnt signaling pathway and one of its known functions is to regulate the levels of β-catenin. Alterations in β-catenin regulation are very common in human tumors [1]. Loss of APC is associated with stabilization of the cytosolic β-catenin that ultimately results in its migration to the nucleus and activating a cascade of events leading to tumorigenesis. APC also interacts with a multitude of other cellular proteins, including axin-2 (AXIN2), plakoglobin (JUP), Asef (ARHGEF4), kinesin superfamily–associated protein 3 (KIFAP3), EB1 (MAPRE1), microtubules, and the human homolog of Drosophila discs large (DLG1). These interactions suggest that APC can potentially regulate many cellular functions, including intercellular adhesion, cytoskeletal organization, regulation of plakoglobin levels, regulation of the cell cycle and apoptosis, orientation of asymmetric stem cell division, and control of cell polarization [2,3]. APC is a tumor suppressor gene. Somatic mutations in APC are frequently found in many sporadic tumors of the colon and rectum. Autosomal dominant germline mutations in APC cause familial adenomatous polypois (FAP) and its variant, Gardner syndrome. FAP patients are characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer in the third and fourth decades of life [4,5]. In addition to colorectal neoplams, these individuals can develop extracolonic symptoms, among which are upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, disorders of the maxillary and skeletal bones, and dental abnormalities [6], suggesting the importance of APC gene functions in these organ systems. Although the role of APC in the initiation of human colorectal cancer is well established, its role in other tissue and developmental processes are not well understood. Given the importance of regulation of Wnt signaling in embryonic pattern formation and morphogenesis of many organs, mechanistic understanding of APC in development and in extracolonic tissues becomes critical to better assess potential adverse events in humans. One approach to understand the role of Apc in development is to develop mice with an inactivating Apc mutation. Several genetically modified mouse strains for Apc have been described [7–10]. Most of these models, in the heterozygous state, show a gastrointestinal and other tumor predisposition phenotype [7–10]. Mouse embryos that are homozygous for the genetic modification die during embryogenesis, and some of the models do not survive beyond gastrulation [8,11]. An alternate approach to understand the role of Apc in development and/or in specific tissues is to generate a mouse strain that carries a conditionally modified allele and mate it with a mouse strain that facilitates the modification of the conditional allele in specific cell lineages. To assess the role of Apc in different stages of life systematically, we generated mice containing a conditional knockout (CKO) mutant allele of Apc (ApcCKO). These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. We report here that K14 promoter-driven loss of Apc resulted in aberrant development of several organs that require inductive epithelial–mesenchymal interactions, including hair follicle, teeth, and thymus, and resulted in neonatal death in mice. We found that Apc plays a crucial role in determinations of cell fates during the embryonic development, possibly via temporal and tissue-specific regulation of β-catenin levels in the skin, its appendages, and in the thymus. Results Generation of the ApcCKO and ApcΔ580 Mice To investigate the role of Apc in development of skin and its appendages, we used the Cre/loxP technology to introduce a conditional mutation of the Apc gene in mice. We constructed embryonic stem (ES) cells and mice carrying an Apc allele harboring both a pair of loxP sites flanking Apc exon 14 and a pair of FLP recognition target (FRT) sites flanking PGK-neomycin selection cassette by recombineering [12,13] (Figure 1A, ApcCKON allele, N for neomycin cassette). A PGK-neomycin cassette was inserted in the same transcriptional orientation as Apc in intron 14 of the endogenous gene. The loxP and FRT sites were used to aid unidirectional recombination [12,13]. Two mouse lines containing the same modification were generated from two independent ES clones to ensure that these two lines behave in the same way. These ApcCKON/+ mice were crossed with FLPe-deleter to generate ApcCKO/+ mice that were heterozygous for the final Apc conditional (ApcCKO) allele that removed the PGK-neomycin cassette and contains only the loxP sites in the introns flanking exon 14. To assess the effect of deleting exon 14 in mice, both lines of ApcCKO/+ mice were crossed with the Cre-deleter to generate the germline knockout line of Apc, designated ApcΔ580/+. The mutant allele (ApcΔ580) lacks exon 14 (Figure 1A). The transcript from loss of exon 14 results in a shift in the normal reading frame, resulting in a premature chain termination codon which, if utilized, would result in a truncated polypeptide that is 605 aa in length, of which the first 580 aa correspond to the normal Apc protein. Figure 1 Generation of the Conditional Apc Allele (A) Schematic diagram of exons 14 and 15 of the mouse Apc gene, the targeting vector, and the resulting conditional allele with 2 LoxP sites sandwiching the exon 14. The PGK-neomycin cassette was inserted within intron 14 by recombineering technique. This cassette is sandwiched by 2 FRT sites that could be removed by crossing to FLPe-expressing mice. Positions of PCR primers used for genotyping PCR (F2, R2, R4) and RT-PCR (F546 and R721) are indicated. Positions of probe used for Southern blot analysis with NdeI sites are also shown. Upon Cre-mediated recombination, exon 14 is removed and leads to truncated Apc protein, of which the first 580 aa correspond to the normal. (B) Southern blot analysis of NdeI-digested genomic tail DNA isolated from F1 mice of various Apc mouse lines (ApcCKON, ApcΔ580), hybridized to a 600-bp probe. Tail genomic DNA from ApcCKON F1 mice derived from a modified ES clone showed a 12-kb band for the ApcCKON allele and a 10-kb band for the wild-type allele, whereas genomic DNA from the ApcΔ580 mouse was heterozygous for the ApcΔ580 allele (9.2-kb band). (C) Kaplan-Meier survival plot of ApcCKO/+ mice (thin solid line, n = 39), ApcCKO/CKO mice (thin dotted line, n = 57), ApcΔ580/+ mice (solid line, n = 51), and wild-type littermates (broken line, n = 21). Heterozygosity of the ApcΔ580 allele led to a significantly shortened survival (p < 0.0001), whereas those of heterozygous and homozygous ApcCKO mice had no significant difference to that of wild-type littermates. Southern blot analysis of tail DNA from F1 offspring of both ApcCKON and ApcΔ580 lines confirmed the germline transmission of modified Apc allele (Figure 1B). Mice that are heterozygous for ApcΔ580 mutation are viable but have a significantly reduced lifespan (Figure 1C). These results suggested that deletion of exon 14 indeed results in either loss or abnormal function of the Apc gene product. ApcΔ580/+ mice have median survival of 5 mo of age (Figure 1C), with progressive signs of rectal bleeding and anemia. Similar to the results reported with an independently generated ApcΔ580/+ conditional mouse strain [14], ApcΔ580/+ mice had more than 100 (120 ± 37, n = 11) intestinal tumors at the time of their death (Figure S1). Inactivation of wild-type Apc is an important prerequisite for tumor development. We analyzed 30 intestinal tumors from ApcΔ580/+ mice by in vitro transcription and translation assay, but none of them showed truncated Apc products (unpublished data), indicating that the most likely mechanism of wild-type Apc inactivation is by allelic loss. The mutant allele had to be maintained and transmitted through male mice, as ApcΔ580/+ females were frequently not healthy enough to successfully nurse their own pups because of their tumor burden. ApcCKO/+ mice were intercrossed to generate ApcCKO/CKO offspring. Approximately one-quarter of the offspring (17 of 81) were homozygous for the ApcCKO allele. These mice as well as heterozygous mice for ApcCKO allele are normal, showing no differences in their survival to the wild-type littermates (Figure 1C). We tested whether our ApcCKO allele can compliment the wild-type allele by crossing the ApcCKO/CKO female with ApcΔ580/+ male mouse. The resultant ApcCKO/Δ580 offspring were viable and born in the Mendelian ratio, suggesting that the presence of loxP sites in introns flanking exon 14 have no adverse effect on the function of the Apc gene. K14-Driven Loss of Apc Results in Severe Growth Retardation and Early Lethality To introduce the mutation of Apc into cells expressing K14, we crossed WW6 ES cell–derived [15] ApcCKO/+ mice with K14-cre recombinase mice in FVB background [16]. The K14-cre; ApcCKO/+ mice were normal in appearance and were fertile. K14-cre; ApcCKO/+ males were crossed to ApcCKO/CKO females to avoid the potential deleter effect in oocytes of K14-cre–positive females [17]. The mice were intercrossed thereafter for maintenance; hence, the mice used for analysis were in a mixed background of FVB, 129/S, and C57BL/6 in similar proportions, with minimal contribution of SJ. The K14 promoter is a commonly used epidermal cell promoter because of its expression by the mitotically active cells of the epidermis and its appendages in mature skin [18], but most notably it is active in embryonic ectoderm as early as the single layered ectodermal stage of embryonic day (E) 9.5 [19]. A restricted expression of K14 is also found in thymic epithelial cells (TECs) in the medulla of normal thymus [20]. We genotyped a total of 458 pups (8–10 d old) from 67 litters resulting from crosses between K14-cre; ApcCKO/+ and ApcCKO/CKO mice. The mutant mice of the genotype K14-cre; ApcCKO/CKO (hereafter, KA mutant) were born, but the observed frequency of KA mutants was much less than expected (78 of 458 [17.0%]; p < 0.0005 Chi-square analysis, Table 1). To assess the basis for the neonatal lethality of KA mutants, we monitored three litters from birth to weaning by measuring the body weight of each pup every day. A total of 25 pups were born from three litters, of which 7 (28%) were confirmed to be K14-cre; ApcCKO/CKO by genotyping, indicating that KA mutants were born in the expected Mendelian ratio. The KA mutant pups were nursed normally, and there was milk in their stomachs during the first 2 or 3 d after birth, but they failed to thrive (Figure 2). By postnatal day (P) 8–10, at the time of genotyping, many KA mutant pups were considerably smaller than their littermates (Figure 2B–2F) and some have died at or prior to this age. None of KA mutants survived to weaning age. Table 1 Genotype Distribution of Progeny from the Matings Figure 2 Postnatal Mortality and Stunted Growth in K14-cre; ApcCKO/CKO Mutant Mice Animals whose genotype is either heterozygous or homozygous for the wild-type Apc allele are referred to as normal (N); those whose genotype are K14-cre; ApcCKO/CKO and show the presence of K14-cre–recombined mutant Apc allele are called mutant (M). (A) Two P3 mutant mice, M1 and M2, and their normal littermates, showing size variation among mutants. (B) P8 mutant mouse (right) and a normal littermate. Note sparseness of hair coat and abnormal ears. (C–D) Vibrissae of whisker pads are short and oddly angled in a P12 mutant mouse (C), relative to control (D). Note the lack of incisors in the mutant. (E) A P17 mutant mouse (right) with its littermate. Its bare forehead, dorsal median line, and abnormal ears are evident. (F) Growth curve of mutants and normal littermates. Mutants exhibit stunted growth, which became more prominent as they aged, and weigh significantly less than littermates from P8 (p < 0.05). (G) Comparison of mutant and normal thymus from P3 mice. The mutant thymus (left) is dramatically smaller for its age compared to the normal littermate (right). The scale bar equals 1 mm. (H) Skeletal preparations of normal (left) and mutant (right), showing differences in development of both incisor (I) and molar (M) teeth. The ability of whole embryos to exclude blue dye was used to examine the epidermal barrier, normally acquired beginning at E16 and complete by E18.5 [21]. Analyses of E17.5–E18.5 KA mutants showed that they were able to exclude blue dye, indicating that the epidermal barrier was intact (Figure S2). At these embryonic ages, there were no differences in size between the mutants and their littermates, but the mutants showed a patch of “birthmark” or dark pigmentation on their foreheads and a dark median line that ran caudally from head to tail. Their external ears or pinnae were shriveled in appearance and pigmented compared to those of littermates. External characteristics of KA mutants that were evident at E18.5 persisted after birth and became more prominent as they grew (Figure 2A–2F). Growth of pelage hair was generally delayed in the mutants. At around P8, the KA mutants were hairless and had wrinkled skin while their phenotypically normal littermates had a smooth thin coat of hair (Figure 2B). At this age, two lower incisors start to erupt in normal littermates and these were absent in the KA mutants (Figure 2C and 2D). Animals also tended to be smaller and around P10–P12 displayed abnormally short and misshapen vibrissae and short, shaggy pelage hairs (Figure 2C and 2D). Development of thick ridges in their skin, particularly around the ears, eyelids, forehead, nose, and paws, became noticeable (Figure 2E). These regions looked scaly, and these animals hardly kept their eyes open. In contrast to the normal littermates that consistently increased their body weight with age, surviving KA mutants started to lose weight from P10 onwards; by P16–P17 they were all lethargic, and none of them survived to weaning (Figure 2E and 2F). At the time of autopsy all the mutants were toothless, without incisors or molars, and their stomachs were consistently small and had no solid food, unlike their age-matched littermates, suggesting that the observed weight loss could be the result of failure to ingest solid food (Figure 2F). Interestingly, changes in body weights and timing of hair growth varied considerably among mutant pups even if they were from the same litter, whereas those of phenotypically normal littermates tended to be similar. This difference was also reflected in the variation in timing of death in mutants: some mutant pups were born alive but died within a day or two, some survived close to the weaning age. This variability of the mutant phenotypes suggests possible variation in the timing and efficiency of cre-mediated Apc deletion. It is possible that the genetic background has a role to play in this variability. Gross examination of internal organs also showed that the mutants' thymi were consistently inconspicuous and were very small for their age, whereas those of their littermates were very prominent in size (Figure 2G). This difference was evident as early as P3. Quite frequently mutant thymi in P12–P17 mutant mice also contained black deposits within the tissue (unpublished data). Mutant mice were also examined for any skeletal abnormalities by preparing skeletal specimens of P16–P17 mice stained with Alizarin red. No differences between the normal and KA mutant mice in the mandibular bone can be detected, but the mutant mice lacked or had underdeveloped set of maxillary incisors and molars (Figure 2H). We detected no other major skeletal abnormalities. Genotype- and Tissue-Specific Expression of the Truncated Apc Transcripts To assess the molecular effects of the K14-cre–mediated recombination, we screened for the presence of deleted Apc (ApcΔ580) alleles. Genomic DNA was extracted from liver, thymus, and skin from all 4 possible genotypes: K14-cre; ApcCKO/CKO, K14-cre; ApcCKO/+, ApcCKO/CKO, and ApcCKO/+. Genotyping on genomic DNA from these tissues showed that the ApcΔ580 allele (500-bp product) was detected only from the skin and thymus of the K14-cre–positive mice. The presence of mutant Apc allele in the thymus of K14-cre; ApcCKO/+ mice was consistently much less than the DNA from the skin of the same animal or other tissues from the KA mutants. In addition, this product was not detected at all in either the liver of K14-cre–positive or in any of the K14-cre–negative mouse tissues samples, establishing that Cre-mediated recombination has taken place in the tissue-specific manner in the mice that inherited K14-cre (Figure 3A). Figure 3 Tissue-Specific Detection and Expression of Deleted Apc Alleles (A) Tissue-specific genotyping PCR. Only genomic DNA samples from the skin (S) and thymus (T), but not liver (L) of mice positive for K14-cre show the presence of deleted ApcΔ580 allele. (B) Genotype- and tissue-specific expression of the truncated Apc transcripts. A representative gel of RT-PCR using primers F546 and R721, showing that only RNA from the skin and thymus but not liver of mice positive for K14-cre have transcripts from both wild-type (528 bp) and deleted (313 bp) Apc alleles. Apc transcripts were also analyzed by RT-PCR with primers spanning exon 14 (Figure 1A) using total RNA isolated from the corresponding tissue samples. We detected the expected RT-PCR product (313 bp) from the truncated Apc (ApcΔ580) allele only in the tissues where Cre recombinase is known to be expressed in the K14-cre–positive mice. However, this product was not detected in either the K14-cre–negative mouse tissues samples or the liver of K14-cre–positive mice, and only the product from the wild-type allele (528 bp) was detected from these RNA samples, further confirming that Cre-mediated recombination has taken place in the tissue- and genotype-specific manner (Figure 3B). K14-cre–Driven Apc Loss Induced Aberrant Hair Follicles throughout the Epidermis To understand the basis for delayed and abnormal hair development in the KA mutants, we conducted a histological and immunohistochemical examination (Figure 4). The hair follicle is an epidermal appendage that consists of an upper permanent portion, and a lower cycling portion that produces the hair [22,23]. The outer root sheath (ORS) is contiguous with and biochemically similar to the basal layer of the epidermis. The inner layers of the hair follicle include three concentric layers of inner root sheath and three concentric layers of hair-producing cells. At the base of the hair follicle is the germinative hair follicle bulb, which contains rapidly proliferating “matrix” cells that differentiate to populate all of the layers of the inner root sheath and the hair shaft itself [22]. During the anagen phase of the hair cycle (until P15), hair follicles of phenotypically normal mice grew deeply into the subcutaneous fat and were uniformly spaced and aligned in parallel arrays at a specific angle relative to the skin surface (Figure 4A). In contrast, KA mutant follicles were irregularly spaced and often seen as disoriented and clamped invaginations at P3 that became even more remarkable at P12 when the mutant mice were covered by fur coat (Figure 4F). Bulbs were often bent in addition to being irregularly angled to one another and their sizes and locations were often variable. Clusters of multiple invaginations or dysplastic follicular structures were frequently observed throughout the epidermis, whereas other regions showed gaps with no follicles. Serial sectioning indicated that some of the hair follicles in the P12 mutant skin were not properly formed or shorter than normal. Taken together, these features could account for the apparently delayed, followed by outgrowth, of the short and shaggy-looking fur coat of these mutant mice. Figure 4 Histological and Immunochemical Examination of P12 Skin and Teeth (A–E) P12 normal skin. (F–J) P12 mutant skin. (K–N) P12 normal oral cavity. (O–R) P12 mutant oral cavity. Stained with H&E for histology (A, F, K–L, O–P), Ki67 (B, G), β-catenin (C, H, M, Q), K14 (D, I, N, R), and K6 (E, J). Aberrant follicular morphogenesis, characterized by formation of irregularly spaced, nonpolarized hair follicles, in mutant skin is evident. Despite the abnormal histology, proliferation seems to be confined to hair bulb-like structures (arrows in [G], inset [G′] at higher magnification), but in mutant skin (arrows in [H], inset [H′] at higher magnification) and oral cavity (arrows in insets [Q′] at higher magnification) elevated cytosolic localization of β-catenin is detected in some cells. Scale bars: 50 μm for (A–F), (H–J); 250 μm for (K) and (O); 100 μm for (G), (L–N), (P–R); 20 μm for (Q′). Apc is a regulator of β-catenin that is important for Wnt signaling. We examined the patterns of expression of β-catenin in the affected tissues. In the normal skin, β-catenin, a member of the adherens junction complex, was found in the ORS of hair follicles and basal layer of epidermis, where K14 expression is also observed (Figure 4C and 4D), whereas the expression of K1, involucrin, and loricrin (markers for spinous and granular layers of epidermis) was only observed in the nonbasal epidermis (unpublished data). The patterns of expression of K14, K1, involucrin, and loricrin, in skin from mutant and normal littermate mice at P3–P17, showed no significant differences in the terminal differentiation (Figure 4A–4D, 4F–4I). Similarly, the pattern of expression of K6, which is normally only expressed in the suprabasal or inner layer of the ORS of the hair follicle but not in the epidermis (Figure 4E), did not change. Due to the abnormal and disorganized structure of hair follicles themselves, K6 localization highlighted the histological abnormality (Figure 4J). Yet as in the normal skin, K6 was principally seen only in the suprabasal layer of the ORS that did not colocalize with the basal markers, K14 or K5 (Figure 4I and 4J). In normal skin, proliferating cells were detected in either the basal layer of epidermis or in germinative hair follicle bulbs at the base (Figure 4B). In the mutant skin, either BrdU incorporation or Ki67 expression was observed not only in cells in bulbs at the base of the hair follicle but also in bulb-like structures that were budding out from the ORS of the existing hair follicles (Figure 4G and 4G′). Each budding tip was becoming like a hair follicle bulb containing proliferating cells. Hence, despite the abnormal histology in the mutant skin, proliferation seems to be confined to bulb-like structures as in the normal skin (Figure 4G and 4G′). The exact locations of hair follicle bulbs were not as easy to define for some mutant follicles due to their disorganized structures. Interestingly, in the mutant skin, in addition to diffuse membrane-bound localization as in the normal skin, cells with strong cytosolic β-catenin localization were also observed frequently (Figure 4H and 4H′). These elevated β-catenin–expressing cells were usually surrounded by proliferating cells, forming bulb-like structures. Comparison of immunochemically stained serial sections showed that these intense cytosolic β-catenin stainings were usually found in either K14-positive K1-negative basal epidermis or K14-positive K6-negative basal ORS cells, and are surrounded by proliferating cells. To determine the initiation of hair follicle morphogenesis in these mutants, we examined the expression pattern of Sonic hedgehog (Shh), a factor expressed in hair bulbs in embryonic skin (Figure 5). The aberrant hair follicle morphogenesis is evident as early as E14.5 in mutant embryonic skin, by multiple apolarized expression of Shh throughout the epidermis (Figure 5B), whereas that of control embryos was well polarized and regularly spaced (Figure 5A). With development, control mouse hair follicles invaginate downward in a polarized manner (Figure 5C), whereas those of mutant embryos were completely irregular and apolarized (Figure 5D). It was also noted that the size of each “budding” follicle, as detected by Shh expression, was variable (Figure 5D). The intensity of Shh staining was generally stronger in mutant skin than in the normal skin. The aberrant initiation of multiple hair placodes during early hair follicle morphogenesis was also evident by the whole-mount in situ hybridization (ISH) of E15.5 mutant embryos for β-catenin (Figure 5F and 5F′). The expression pattern of β-catenin in embryos clearly demonstrated the formation of regular arrays of hair placodes in the normal embryonic skin (Figure 5E and 5E′), but such regular patterning was lost, and often tightly clustered abnormal hair placodes were initiated in mutant embryonic skin (Figure 5F′). Aberrant hair placodes were also evident throughout the skin surface of limbs in E15.5 mutants (Figure 5F), whereas those of the control embryos had not yet formed (Figure 5E). Most interestingly, in the mutant footpads, where hair placodes do not normally form (Figure 5G), we also found ectopic irregularly sized and spaced hair placodes, indicating that the footpads still have the potential to form hair placodes in the absence of the Apc gene (Figure 5H). Figure 5 Expression of Shh and β-catenin Transcripts in Normal (ApcCKO/CKO) and Mutant (K14-cre; ApcCKO/CKO) Embryonic Skin (A–D) Section ISH with Shh probe in E14.5 normal (A), E14.5 mutant (B), E16.5 normal (C), and E16.5 mutant (D) skin. Broken lines indicate the interface between epithelium and mesenchyme. Scale bars: 50 μm. Whole mount in situ detection of β-catenin in E15.5 normal (E, G), mutant (F, H) embryos. Aberrant initiation of multiple hair placodes is evident at E14.5. Loss of K14-driven Apc loss caused aberrant pattern formation (F′) and formed ectopic hair placodes in normally hairless foot pads (H, arrows) which are absent in normal (G). These results collectively suggest that the terminal differentiation does take place normally in the mutant skin, but initiation of embryonic hair follicle morphogenesis is severely disrupted, accompanied by a continuous ectopic hair follicle morphogenesis in postnatal mutant skin. Effects of K14-cre–Driven Loss of Apc in Other Epidermal Appendages Similar to the biology of hair follicles, K14-cre–driven loss of Apc also affected the development of other epidermal appendages that depend on epithelial–mesenchymal interactions for their formation. The most striking of these was dental dysplasia (Figure 4K–4R). Tooth development is normally initiated between E11 and E12 by invagination of ectodermally derived oral epithelium into the underlying cranial neural crest–derived mesenchyme, generating a tooth germ. Despite the grossly toothless phenotype of KA mutants, histological analysis of their oral cavities revealed the formation of multiple tooth buds at each location. These aberrant teeth obviously failed to grow out during the dietary transition from milk to solid food. Analogous to the expression patterns of K14 and β-catenin in the normal skin, diffuse membrane-bound expression of β-catenin was detected in K14-expressing oral epithelium and ameloblasts of normal mice. In mutants, some of the K14-expressing cells also showed strong cytosolic/nuclear β-catenin staining, as observed in the mutant skin (Figure 4Q, 4Q′, and 4R). Initiation of ectopic tooth buds in the mutant mice was evident at E15.5 by extra dots of Shh expression adjacent to the primary teeth (data not shown). Loss of Apc also leads to hyperplasia in squamous epithelia of cornea, oral, salivary, and Hardarian glands (unpublished data). Squamous metaplasia to hair follicle–like structures, ectopic hair follicle morphogenesis was also observed in these epithelia. K14-cre–Driven Apc Loss Results in Hypoplastic/Athymic Mice Thymus is an organ that is also known to have K14 expression [16]. It represents the primary lymphoid organ for thymocyte development and selection. Distinct population of TECs of cortex and medulla mediates both of these critical functions. Cortical and medullary TEC subsets are characterized by differential expression of four keratin species: K8, K18, K5, and K14. The normal thymus is a lobulated lymphoid organ, each lobule clearly showing the two distinct TEC compartments, an outer cortex and an inner medulla (Figure 6). There were no major differences in the histology of thymus between the ages P3 to P17 in phenotypically normal littermates. As shown in the H&E staining of thymus, the cortex was formed of dense lymphoid tissue that lacks nodules (Figure 6A). Since the stroma of the medulla is less heavily infiltrated with lymphocytes than the cortex, the medulla stained more lightly than the cortex. In normal mice, the thymus retains its size until the young adult age and regresses thereafter by atrophy. In the normal young mice we examined (P3–P17), it is evident that thymocytes were mitotically active in the cortex as determined by BrdU immunostaining (Figure 6B). Immunohistochemistry of normal thymus from P3 to P17 mice showed a similar staining pattern for K14 in that its expression was restricted to a small population of TECs in the inner medullary region and in the keratinocytes in Hassall's corpuscles (Figure 6D). Diffuse cytoplasmic staining for β-catenin was also detected in the medullary epithelial cells (Figure 6C). In contrast to K14 expression, diffuse staining for K8 was observed in epithelial cells both in the medulla and cortex (Figure S3). K1 staining was not detected in young mice at P3 but in older mice it was detected in differentiated keratinocytes in some of Hassall's corpuscles (Figure S3). Figure 6 Histological and Immunochemical Examination of Thymus (A–D) P3 normal thymus. (E–G) Mild P3 mutant thymus. (H–K) Severe P3 mutant thymus. (L–O) P13 mutant thymus. Stained with H&E for histology (A, E, H, L), BrdU (B, I, M), β-catenin (C, F, J, N), and K14 (D, G, K, O). (B) Actively dividing thymocytes are visible at the superficial edge of cortex of normal P3 thymus. Note the progression of histological abnormalities in the mutant thymus from mild P3, severe P3 to P13 (A, E, H, L). Scale bars, 20 μm. The histological abnormalities of thymus were evident as early as P3 in KA mutants (Figure 6E and 6H). The thymus was made of two lobules as in the normal mice but the mutant thymus was significantly smaller in size than that of the age-matched controls (Figure 2G). Interestingly, variations in the phenotypic severity of the mutant pups at P3 were prominently reflected in the extent of histological abnormalities of thymus. A P3 KA mutant pup that showed milder phenotype with a comparable body weight to its normal littermates (Figure 2A, M2) showed milder thymus abnormalities (Figure 6E) compared to its more severe mutant littermate (Figure 2A, M1; Figure 6H). The milder P3 mutant thymus was already much smaller in size compared to those of normal littermates (data not shown) but two epithelial compartments of thymus were histologically still distinguishable, with colonization of thymocytes evident in the cortex. However, there were small populations of lightly stained cells by H&E extending from the edge of the outer cortex towards inner medulla (Figure 6E), and these cells showed intense nuclear β-catenin staining whereas the rest of the medullary cells showed diffuse β-catenin staining pattern similar to that of the control (Figure 6F). Localization of K14 was limited to a few cells in the medulla and some overlapped with K8 localization (Figure 6G). In the other P3 mutant thymus the distinct thymic epithelial compartments have been lost completely, and only a few lymphocytes were remaining at the edges and some in the middle (Figure 6H). Proliferative activities were no longer observed in thymocytes as prominently as in the normal thymus, but the epithelial cells seemed to be forming concentric structures (Figure 6I). Unlike in the normal or mild mutant thymi, the severe P3 mutant thymus showed extensive K14 expression that overlapped with K8 expression (Figure 6K). These cells were more like basal cells of the skin than TECs and were adjacent to the most immature looking cells that were showing strong nuclear and cytoplasmic β-catenin staining (Figure 6J). The nuclear staining of β-catenin was not observed in the normal age-matched thymus (Figure 6C). Most notably, the K14 and β-catenin staining patterns were mutually exclusive (Figure 6J and 6K). At P10–P13, the mutant thymus consisted of numerous enlarged Hassall's corpuscle–like structures, made of arrays of K14- and K8-expressing keratinizing epithelial cells surrounding large keratin deposits (Figure 6L and 6O). There were numerous neutrophils and macrophages infiltrating the thymus in response to these keratins; hence, these structures could be called pyogranuloma. Varying degrees of differentiation-specific markers depending on the age of mice, in this case K1 and involucrin that are normally present only in Hassall's corpuscles, were also detected in mutant thymi (Figure S3). In these mice no thymocytes were detectable. BrdU incorporation was only observed in very few keratinizing epithelial cells, looking somewhat similar to the pattern of mature skin (Figure 6M). The diffuse expression of β-catenin was also present in these epithelial cells, and at this age fewer cells were positive for nuclear β-catenin staining (Figure 6N). As in the younger mutant mice, however, nuclear localization of β-catenin was only observed in K14-negative cells that looked like undifferentiated basal cells. In older P17 mice, the histopathology and keratin expression pattern of the mutant thymus was similar to that of P13 except for the fact that β-catenin expression became increasingly diffuse and appeared to colocalize with K8/K14 expression (data not shown). This coincided with fewer immature cells in the older mutant thymus. Collectively, these results suggest that loss of Apc and consequent stabilization of β-catenin in K14-expressing TECs lead to their aberrant proliferation and differentiation to keratinocytes, causing massive squamous metaplasia, rather than to form either medullary or cortical TECs. Loss of proper TEC compartments consequently resulted in loss of thymocytes for maturation and the mice to be “athymic.” Discussion Apc ",implicated
R5655 T19066 T19065 auxpass is,implicated
R5656 T19067 T19065 prep in,implicated
R5657 T19068 T19069 det the,pathway
R5658 T19069 T19067 pobj pathway,in
R5659 T19070 T19069 compound Wnt,pathway
R5660 T19071 T19069 compound signaling,pathway
R5661 T19072 T19073 dep that,involved
R5662 T19073 T19069 relcl involved,pathway
R5663 T19074 T19073 auxpass is,involved
R5664 T19075 T19076 preconj both,in
R5665 T19076 T19073 prep in,involved
R5666 T19077 T19076 pobj development,in
R5667 T19078 T19077 cc and,development
R5668 T19079 T19077 conj tumorigenesis,development
R5669 T19080 T19065 punct .,implicated
R5670 T19082 T19083 amod Human,mutations
R5671 T19083 T19085 nsubj mutations,cause
R5672 T19084 T19083 compound germline,mutations
R5673 T19086 T19083 prep in,mutations
R5674 T19087 T19086 pobj APC,in
R5675 T19088 T19085 dobj FAP,cause
R5676 T19089 T19090 punct [,5
R5677 T19090 T19088 parataxis 5,FAP
R5678 T19091 T19090 nummod 4,5
R5679 T19092 T19090 punct ",",5
R5680 T19093 T19090 punct ],5
R5681 T19094 T19088 punct ", ",FAP
R5682 T19095 T19096 dep which,characterized
R5683 T19096 T19088 relcl characterized,FAP
R5684 T19097 T19096 auxpass is,characterized
R5685 T19098 T19096 agent by,characterized
R5686 T19099 T19098 pobj hundreds,by
R5687 T19100 T19099 prep of,hundreds
R5688 T19101 T19102 amod adenomatous,polyps
R5689 T19102 T19100 pobj polyps,of
R5690 T19103 T19102 amod colorectal,polyps
R5691 T19104 T19088 punct ", ",FAP
R5692 T19105 T19088 prep with,FAP
R5693 T19106 T19107 det an,progression
R5694 T19107 T19105 pobj progression,with
R5695 T19108 T19109 advmod almost,inevitable
R5696 T19109 T19107 amod inevitable,progression
R5697 T19110 T19107 prep to,progression
R5698 T19111 T19112 amod colorectal,cancer
R5699 T19112 T19110 pobj cancer,to
R5700 T19113 T19107 prep in,progression
R5701 T19114 T19115 det the,decades
R5702 T19115 T19113 pobj decades,in
R5703 T19116 T19115 amod third,decades
R5704 T19117 T19116 cc and,third
R5705 T19118 T19116 conj fourth,third
R5706 T19119 T19115 prep of,decades
R5707 T19120 T19119 pobj life,of
R5708 T19121 T19085 punct .,cause
R5709 T19123 T19124 det The,features
R5710 T19124 T19126 nsubj features,be
R5711 T19125 T19124 amod phenotypical,features
R5712 T19127 T19124 prep of,features
R5713 T19128 T19127 pobj FAP,of
R5714 T19129 T19128 cc and,FAP
R5715 T19130 T19131 poss its,variant
R5716 T19131 T19128 conj variant,FAP
R5717 T19132 T19131 punct ", ",variant
R5718 T19133 T19134 poss Gardner,syndrome
R5719 T19134 T19131 appos syndrome,variant
R5720 T19135 T19133 case 's,Gardner
R5721 T19136 T19126 punct ", ",be
R5722 T19137 T19126 aux can,be
R5723 T19138 T19139 advmod very,variable
R5724 T19139 T19126 acomp variable,be
R5725 T19140 T19126 punct .,be
R5726 T19142 T19143 advmod As,as
R5727 T19143 T19145 cc as,polyps
R5728 T19144 T19143 advmod well,as
R5729 T19145 T19147 dep polyps,develop
R5730 T19146 T19145 amod colorectal,polyps
R5731 T19148 T19147 punct ", ",develop
R5732 T19149 T19150 det these,individuals
R5733 T19150 T19147 nsubj individuals,develop
R5734 T19151 T19147 aux can,develop
R5735 T19152 T19153 amod extracolonic,symptoms
R5736 T19153 T19147 dobj symptoms,develop
R5737 T19154 T19153 punct ", ",symptoms
R5738 T19155 T19156 prep among,are
R5739 T19156 T19153 relcl are,symptoms
R5740 T19157 T19155 pobj which,among
R5741 T19158 T19159 amod upper,tract
R5742 T19159 T19161 compound tract,polyps
R5743 T19160 T19159 amod gastrointestinal,tract
R5744 T19161 T19156 nsubj polyps,are
R5745 T19162 T19161 punct ", ",polyps
R5746 T19163 T19164 amod congenital,hypertrophy
R5747 T19164 T19161 conj hypertrophy,polyps
R5748 T19165 T19164 prep of,hypertrophy
R5749 T19166 T19167 det the,epithelium
R5750 T19167 T19165 pobj epithelium,of
R5751 T19168 T19167 amod retinal,epithelium
R5752 T19169 T19167 compound pigment,epithelium
R5753 T19170 T19164 punct ", ",hypertrophy
R5754 T19171 T19172 amod desmoid,tumors
R5755 T19172 T19164 conj tumors,hypertrophy
R5756 T19173 T19172 punct ", ",tumors
R5757 T19174 T19172 conj disorders,tumors
R5758 T19175 T19174 prep of,disorders
R5759 T19176 T19177 det the,bones
R5760 T19177 T19175 pobj bones,of
R5761 T19178 T19177 amod maxillary,bones
R5762 T19179 T19178 cc and,maxillary
R5763 T19180 T19178 conj skeletal,maxillary
R5764 T19181 T19174 punct ", ",disorders
R5765 T19182 T19174 cc and,disorders
R5766 T19183 T19184 amod dental,abnormalities
R5767 T19184 T19174 conj abnormalities,disorders
R5768 T19185 T19186 punct [,6
R5769 T19186 T19147 parataxis 6,develop
R5770 T19187 T19186 punct ],6
R5771 T19188 T19147 punct .,develop
R5772 T19190 T19191 mark While,develop
R5773 T19191 T19198 advcl develop,die
R5774 T19192 T19193 det the,mice
R5775 T19193 T19191 nsubj mice,develop
R5776 T19194 T19195 amod heterozygous,knockout
R5777 T19195 T19193 compound knockout,mice
R5778 T19196 T19193 prep for,mice
R5779 T19197 T19196 pobj Apc,for
R5780 T19199 T19200 amod adenomatous,polyps
R5781 T19200 T19191 dobj polyps,develop
R5782 T19201 T19202 advmod predominantly,in
R5783 T19202 T19191 prep in,develop
R5784 T19203 T19204 amod small,intestine
R5785 T19204 T19202 pobj intestine,in
R5786 T19205 T19198 punct ", ",die
R5787 T19206 T19207 det the,embryos
R5788 T19207 T19198 nsubj embryos,die
R5789 T19208 T19207 amod homozygous,embryos
R5790 T19209 T19198 prep before,die
R5791 T19210 T19209 pobj gastrulation,before
R5792 T19211 T19198 punct .,die
R5793 T19213 T19214 aux To,gain
R5794 T19214 T19215 advcl gain,created
R5795 T19216 T19217 amod more,insights
R5796 T19217 T19214 dobj insights,gain
R5797 T19218 T19217 prep into,insights
R5798 T19219 T19220 det the,effects
R5799 T19220 T19218 pobj effects,into
R5800 T19221 T19220 prep of,effects
R5801 T19222 T19223 compound Apc,loss
R5802 T19223 T19221 pobj loss,of
R5803 T19224 T19220 prep in,effects
R5804 T19225 T19224 pobj tissues,in
R5805 T19226 T19225 amod other,tissues
R5806 T19227 T19226 prep than,other
R5807 T19228 T19229 amod gastrointestinal,tract
R5808 T19229 T19227 pobj tract,than
R5809 T19230 T19220 prep during,effects
R5810 T19231 T19230 pobj life,during
R5811 T19232 T19231 prep of,life
R5812 T19233 T19232 pobj animals,of
R5813 T19234 T19214 cc and,gain
R5814 T19235 T19236 aux to,circumvent
R5815 T19236 T19214 conj circumvent,gain
R5816 T19237 T19238 det the,lethality
R5817 T19238 T19236 dobj lethality,circumvent
R5818 T19239 T19238 amod embryonic,lethality
R5819 T19240 T19238 acl associated,lethality
R5820 T19241 T19240 prep with,associated
R5821 T19242 T19243 compound Apc,nullizygosity
R5822 T19243 T19241 pobj nullizygosity,with
R5823 T19244 T19215 punct ", ",created
R5824 T19245 T19215 nsubj we,created
R5825 T19246 T19247 det a,strain
R5826 T19247 T19215 dobj strain,created
R5827 T19248 T19247 compound mouse,strain
R5828 T19249 T19247 acl carrying,strain
R5829 T19250 T19251 det a,allele
R5830 T19251 T19249 dobj allele,carrying
R5831 T19252 T19251 amod conditional,allele
R5832 T19253 T19251 prep of,allele
R5833 T19254 T19253 pobj Apc,of
R5834 T19255 T19256 punct (,ApcCKO
R5835 T19256 T19251 parataxis ApcCKO,allele
R5836 T19257 T19256 punct ),ApcCKO
R5837 T19258 T19259 prep in,flanked
R5838 T19259 T19251 relcl flanked,allele
R5839 T19260 T19258 pobj which,in
R5840 T19261 T19259 nsubjpass exon,flanked
R5841 T19262 T19261 nummod 14,exon
R5842 T19263 T19261 prep of,exon
R5843 T19264 T19265 det the,Apc
R5844 T19265 T19263 pobj Apc,of
R5845 T19266 T19259 auxpass is,flanked
R5846 T19267 T19259 agent by,flanked
R5847 T19268 T19269 compound loxP,sequences
R5848 T19269 T19267 pobj sequences,by
R5849 T19270 T19215 punct .,created
R5850 T19272 T19273 det The,mice
R5851 T19273 T19275 nsubj mice,are
R5852 T19274 T19273 amod homozygous,mice
R5853 T19276 T19273 prep for,mice
R5854 T19277 T19278 det the,allele
R5855 T19278 T19276 pobj allele,for
R5856 T19279 T19278 amod conditional,allele
R5857 T19280 T19275 acomp viable,are
R5858 T19281 T19280 cc and,viable
R5859 T19282 T19280 conj indistinguishable,viable
R5860 T19283 T19282 prep to,indistinguishable
R5861 T19284 T19285 det the,mice
R5862 T19285 T19283 pobj mice,to
R5863 T19286 T19285 amod normal,mice
R5864 T19287 T19275 punct ", ",are
R5865 T19288 T19275 advcl allowing,are
R5866 T19289 T19290 nsubj us,study
R5867 T19290 T19288 ccomp study,allowing
R5868 T19291 T19290 aux to,study
R5869 T19292 T19293 det the,roles
R5870 T19293 T19290 dobj roles,study
R5871 T19294 T19293 prep of,roles
R5872 T19295 T19294 pobj Apc,of
R5873 T19296 T19290 prep in,study
R5874 T19297 T19298 det a,manner
R5875 T19298 T19296 pobj manner,in
R5876 T19299 T19300 npadvmod tissue,specific
R5877 T19300 T19298 amod specific,manner
R5878 T19301 T19299 punct -,tissue
R5879 T19302 T19299 cc and,tissue
R5880 T19303 T19299 conj temporal,tissue
R5881 T19304 T19300 punct -,specific
R5882 T19305 T19275 punct .,are
R5883 T19307 T19308 aux To,assess
R5884 T19308 T19309 advcl assess,created
R5885 T19310 T19311 det the,consequences
R5886 T19311 T19308 dobj consequences,assess
R5887 T19312 T19311 amod phenotypic,consequences
R5888 T19313 T19311 prep of,consequences
R5889 T19314 T19313 pobj inactivation,of
R5890 T19315 T19314 prep of,inactivation
R5891 T19316 T19317 det the,gene
R5892 T19317 T19315 pobj gene,of
R5893 T19318 T19317 compound Apc,gene
R5894 T19319 T19308 prep in,assess
R5895 T19320 T19319 pobj cells,in
R5896 T19321 T19322 dep that,express
R5897 T19322 T19320 relcl express,cells
R5898 T19323 T19322 dobj K14,express
R5899 T19324 T19309 punct ", ",created
R5900 T19325 T19309 nsubj we,created
R5901 T19326 T19309 dobj mice,created
R5902 T19327 T19328 dep that,are
R5903 T19328 T19326 relcl are,mice
R5904 T19329 T19328 acomp homozygous,are
R5905 T19330 T19329 prep for,homozygous
R5906 T19331 T19332 det the,allele
R5907 T19332 T19330 pobj allele,for
R5908 T19333 T19332 compound ApcCKO,allele
R5909 T19334 T19328 cc and,are
R5910 T19335 T19328 conj contain,are
R5911 T19336 T19337 det a,transgene
R5912 T19337 T19335 dobj transgene,contain
R5913 T19338 T19339 compound K14,cre
R5914 T19339 T19337 compound cre,transgene
R5915 T19340 T19339 punct -,cre
R5916 T19341 T19309 punct .,created
R5917 T19343 T19344 det These,mice
R5918 T19344 T19345 nsubj mice,failed
R5919 T19346 T19347 aux to,thrive
R5920 T19347 T19345 xcomp thrive,failed
R5921 T19348 T19345 cc and,failed
R5922 T19349 T19345 conj died,failed
R5923 T19350 T19349 prep before,died
R5924 T19351 T19350 pobj weaning,before
R5925 T19352 T19345 punct .,failed
R5926 T19354 T19355 nsubj They,exhibited
R5927 T19356 T19355 advmod also,exhibited
R5928 T19357 T19358 nmod hair,phenotypes
R5929 T19358 T19355 dobj phenotypes,exhibited
R5930 T19359 T19357 punct ", ",hair
R5931 T19360 T19357 conj tooth,hair
R5932 T19361 T19360 punct ", ",tooth
R5933 T19362 T19360 cc and,tooth
R5934 T19363 T19360 conj thymus,tooth
R5935 T19364 T19355 punct .,exhibited
R5954 T22183 T22184 nmod Apc,Morphogenesis
R5955 T22185 T22183 cc and,Apc
R5956 T22186 T22187 compound Hair,Follicle
R5957 T22187 T22183 conj Follicle,Apc
R5958 T22189 T22190 amod Current,models
R5959 T22190 T22191 nsubj models,suggest
R5960 T22192 T22190 prep of,models
R5961 T22193 T22194 compound hair,follicle
R5962 T22194 T22195 compound follicle,development
R5963 T22195 T22192 pobj development,of
R5964 T22196 T22197 mark that,achieved
R5965 T22197 T22191 ccomp achieved,suggest
R5966 T22198 T22199 det the,establishment
R5967 T22199 T22197 nsubjpass establishment,achieved
R5968 T22200 T22199 prep of,establishment
R5969 T22201 T22202 det a,array
R5970 T22202 T22200 pobj array,of
R5971 T22203 T22202 amod regular,array
R5972 T22204 T22202 prep of,array
R5973 T22205 T22204 pobj placodes,of
R5974 T22206 T22202 prep in,array
R5975 T22207 T22208 det the,epithelium
R5976 T22208 T22206 pobj epithelium,in
R5977 T22209 T22208 compound surface,epithelium
R5978 T22210 T22199 prep in,establishment
R5979 T22211 T22210 pobj response,in
R5980 T22212 T22211 prep to,response
R5981 T22213 T22214 det the,message
R5982 T22214 T22212 pobj message,to
R5983 T22215 T22214 amod first,message
R5984 T22216 T22214 amod dermal,message
R5985 T22217 T22197 auxpass is,achieved
R5986 T22218 T22197 prep through,achieved
R5987 T22219 T22220 det the,activities
R5988 T22220 T22218 pobj activities,through
R5989 T22221 T22220 amod competing,activities
R5990 T22222 T22220 prep of,activities
R5991 T22223 T22222 pobj molecules,of
R5992 T22224 T22225 dep that,promote
R5993 T22225 T22223 relcl promote,molecules
R5994 T22226 T22225 cc or,promote
R5995 T22227 T22225 conj repress,promote
R5996 T22228 T22229 compound placode,fate
R5997 T22229 T22227 dobj fate,repress
R5998 T22230 T22231 punct [,24
R5999 T22231 T22191 parataxis 24,suggest
R6000 T22232 T22231 punct ],24
R6001 T22233 T22191 punct .,suggest
R6002 T22235 T22236 expl There,is
R6003 T22237 T22238 amod accumulating,evidence
R6004 T22238 T22236 attr evidence,is
R6005 T22239 T22240 mark that,involved
R6006 T22240 T22238 acl involved,evidence
R6007 T22241 T22240 nsubjpass activation,involved
R6008 T22242 T22241 prep of,activation
R6009 T22243 T22244 det the,pathway
R6010 T22244 T22242 pobj pathway,of
R6011 T22245 T22244 compound Wnt,pathway
R6012 T22246 T22244 compound signaling,pathway
R6013 T22247 T22241 prep in,activation
R6014 T22248 T22249 det the,dermis
R6015 T22249 T22247 pobj dermis,in
R6016 T22250 T22240 aux may,involved
R6017 T22251 T22240 auxpass be,involved
R6018 T22252 T22240 prep in,involved
R6019 T22253 T22252 pcomp establishing,in
R6020 T22254 T22255 det the,signal
R6021 T22255 T22253 dobj signal,establishing
R6022 T22256 T22255 amod first,signal
R6023 T22257 T22255 amod dermal,signal
R6024 T22258 T22236 punct .,is
R6025 T22260 T22261 amod Experimental,activation
R6026 T22261 T22262 nsubj activation,induces
R6027 T22263 T22261 prep of,activation
R6028 T22264 T22265 amod epithelial,signaling
R6029 T22265 T22263 pobj signaling,of
R6030 T22266 T22267 compound β,catenin
R6031 T22267 T22265 compound catenin,signaling
R6032 T22268 T22267 punct -,catenin
R6033 T22269 T22261 punct (,activation
R6034 T22270 T22261 prep by,activation
R6035 T22271 T22270 pobj expression,by
R6036 T22272 T22271 prep of,expression
R6037 T22273 T22274 compound N,terminal
R6038 T22274 T22276 npadvmod terminal,truncated
R6039 T22275 T22274 punct -,terminal
R6040 T22276 T22278 amod truncated,forms
R6041 T22277 T22276 punct –,truncated
R6042 T22278 T22272 pobj forms,of
R6043 T22279 T22278 punct ", ",forms
R6044 T22280 T22281 advmod constitutively,stabilized
R6045 T22281 T22278 amod stabilized,forms
R6046 T22282 T22278 prep of,forms
R6047 T22283 T22284 compound β,catenin
R6048 T22284 T22282 pobj catenin,of
R6049 T22285 T22284 punct -,catenin
R6050 T22286 T22271 cc or,expression
R6051 T22287 T22288 amod ectopic,expression
R6052 T22288 T22271 conj expression,expression
R6053 T22289 T22288 prep of,expression
R6054 T22290 T22289 pobj Lef1,of
R6055 T22291 T22262 punct ),induces
R6056 T22292 T22293 amod ectopic,follicles
R6057 T22293 T22262 dobj follicles,induces
R6058 T22294 T22262 prep in,induces
R6059 T22295 T22296 preconj both,mouse
R6060 T22296 T22297 nmod mouse,skin
R6061 T22297 T22294 pobj skin,in
R6062 T22298 T22296 cc and,mouse
R6063 T22299 T22296 conj chick,mouse
R6064 T22300 T22301 punct [,25
R6065 T22301 T22262 parataxis 25,induces
R6066 T22302 T22303 punct –,27
R6067 T22303 T22301 prep 27,25
R6068 T22304 T22301 punct ],25
R6069 T22305 T22262 punct .,induces
R6070 T22307 T22308 advmod Conversely,results
R6071 T22309 T22308 punct ", ",results
R6072 T22310 T22311 amod down,regulation
R6073 T22311 T22308 nsubj regulation,results
R6074 T22312 T22311 punct -,regulation
R6075 T22313 T22311 prep of,regulation
R6076 T22314 T22315 compound β,catenin
R6077 T22315 T22317 compound catenin,signaling
R6078 T22316 T22315 punct -,catenin
R6079 T22317 T22313 pobj signaling,of
R6080 T22318 T22311 punct (,regulation
R6081 T22319 T22311 prep through,regulation
R6082 T22320 T22321 npadvmod Lef1,knock
R6083 T22321 T22322 amod knock,expression
R6084 T22322 T22319 pobj expression,through
R6085 T22323 T22321 punct -,knock
R6086 T22324 T22321 prt out,knock
R6087 T22325 T22322 punct ", ",expression
R6088 T22326 T22322 amod ectopic,expression
R6089 T22327 T22322 prep of,expression
R6090 T22328 T22329 compound Wnt,inhibitor
R6091 T22329 T22327 pobj inhibitor,of
R6092 T22330 T22329 appos Dkk1,inhibitor
R6093 T22331 T22322 cc or,expression
R6094 T22332 T22333 amod conditional,deletion
R6095 T22333 T22322 conj deletion,expression
R6096 T22334 T22333 prep of,deletion
R6097 T22335 T22336 compound β,catenin
R6098 T22336 T22334 pobj catenin,of
R6099 T22337 T22336 punct -,catenin
R6100 T22338 T22333 prep in,deletion
R6101 T22339 T22338 pobj epidermis,in
R6102 T22340 T22308 punct ),results
R6103 T22341 T22308 prep in,results
R6104 T22342 T22341 pobj loss,in
R6105 T22343 T22342 prep of,loss
R6106 T22344 T22343 pobj vibrissae,of
R6107 T22345 T22344 cc and,vibrissae
R6108 T22346 T22347 det some,follicles
R6109 T22347 T22344 conj follicles,vibrissae
R6110 T22348 T22347 compound pelage,follicles
R6111 T22349 T22308 prep in,results
R6112 T22350 T22349 pobj mice,in
R6113 T22351 T22352 punct [,28
R6114 T22352 T22308 parataxis 28,results
R6115 T22353 T22354 punct –,30
R6116 T22354 T22352 prep 30,28
R6117 T22355 T22352 punct ],28
R6118 T22356 T22308 punct .,results
R6119 T22358 T22359 poss Our,finding
R6120 T22359 T22360 nsubj finding,is
R6121 T22361 T22362 mark that,resulted
R6122 T22362 T22359 acl resulted,finding
R6123 T22363 T22364 npadvmod K14,driven
R6124 T22364 T22366 amod driven,loss
R6125 T22365 T22364 punct -,driven
R6126 T22366 T22362 nsubj loss,resulted
R6127 T22367 T22366 compound Apc,loss
R6128 T22368 T22366 prep in,loss
R6129 T22369 T22370 amod embryonic,ectoderm
R6130 T22370 T22368 pobj ectoderm,in
R6131 T22371 T22362 prep in,resulted
R6132 T22372 T22373 advmod irregularly,spaced
R6133 T22373 T22374 amod spaced,initiation
R6134 T22374 T22371 pobj initiation,in
R6135 T22375 T22373 cc and,spaced
R6136 T22376 T22377 advmod often,clustered
R6137 T22377 T22373 conj clustered,spaced
R6138 T22378 T22377 advmod tightly,clustered
R6139 T22379 T22374 amod abnormal,initiation
R6140 T22380 T22374 compound hair,initiation
R6141 T22381 T22374 compound placode,initiation
R6142 T22382 T22374 cc and,initiation
R6143 T22383 T22384 compound follicle,morphogenesis
R6144 T22384 T22374 conj morphogenesis,initiation
R6145 T22385 T22386 punct (,4F
R6146 T22386 T22374 parataxis 4F,initiation
R6147 T22387 T22386 compound Figures,4F
R6148 T22388 T22386 punct ", ",4F
R6149 T22389 T22386 conj 5B,4F
R6150 T22390 T22389 punct ", ",5B
R6151 T22391 T22389 conj 5D,5B
R6152 T22392 T22391 punct ", ",5D
R6153 T22393 T22391 cc and,5D
R6154 T22394 T22391 conj 5F,5D
R6155 T22395 T22386 punct ),4F
R6156 T22396 T22397 advmod as,as
R6157 T22397 T22371 cc as,in
R6158 T22398 T22397 advmod well,as
R6159 T22399 T22371 conj in,in
R6160 T22400 T22401 det the,development
R6161 T22401 T22399 pobj development,in
R6162 T22402 T22401 prep of,development
R6163 T22403 T22404 amod multiple,buds
R6164 T22404 T22402 pobj buds,of
R6165 T22405 T22404 compound tooth,buds
R6166 T22406 T22407 punct (,4O
R6167 T22407 T22404 parataxis 4O,buds
R6168 T22408 T22407 compound Figure,4O
R6169 T22409 T22407 cc and,4O
R6170 T22410 T22407 conj 4P,4O
R6171 T22411 T22407 punct ),4O
R6172 T22412 T22360 punct ", ",is
R6173 T22413 T22360 prep in,is
R6174 T22414 T22413 pobj line,in
R6175 T22415 T22414 prep with,line
R6176 T22416 T22417 det the,effects
R6177 T22417 T22415 pobj effects,with
R6178 T22418 T22417 acl seen,effects
R6179 T22419 T22418 prep in,seen
R6180 T22420 T22419 pobj activation,in
R6181 T22421 T22420 prep of,activation
R6182 T22422 T22423 amod epithelial,signaling
R6183 T22423 T22421 pobj signaling,of
R6184 T22424 T22425 compound β,catenin
R6185 T22425 T22423 compound catenin,signaling
R6186 T22426 T22425 punct -,catenin
R6187 T22427 T22420 prep during,activation
R6188 T22428 T22429 compound placode,formation
R6189 T22429 T22427 pobj formation,during
R6190 T22430 T22360 punct ", ",is
R6191 T22431 T22360 advcl indicating,is
R6192 T22432 T22433 det the,role
R6193 T22433 T22431 dobj role,indicating
R6194 T22434 T22433 prep of,role
R6195 T22435 T22434 pobj Apc,of
R6196 T22436 T22433 prep in,role
R6197 T22437 T22436 pobj specification,in
R6198 T22438 T22437 prep of,specification
R6199 T22439 T22440 amod embryonic,cells
R6200 T22440 T22438 pobj cells,of
R6201 T22441 T22440 amod ectodermal,cells
R6202 T22442 T22440 compound stem,cells
R6203 T22443 T22444 aux to,produce
R6204 T22444 T22437 acl produce,specification
R6205 T22445 T22446 det a,follicle
R6206 T22446 T22444 dobj follicle,produce
R6207 T22447 T22446 compound hair,follicle
R6208 T22448 T22360 punct .,is
R6209 T22450 T22451 prep Given,lead
R6210 T22452 T22453 det the,role
R6211 T22453 T22450 pobj role,Given
R6212 T22454 T22453 prep of,role
R6213 T22455 T22454 pobj Apc,of
R6214 T22456 T22453 prep in,role
R6215 T22457 T22458 advmod down,regulation
R6216 T22458 T22456 pobj regulation,in
R6217 T22459 T22458 punct -,regulation
R6218 T22460 T22458 prep of,regulation
R6219 T22461 T22462 compound β,catenin
R6220 T22462 T22460 pobj catenin,of
R6221 T22463 T22462 punct -,catenin
R6222 T22464 T22451 punct ", ",lead
R6223 T22465 T22451 nsubj loss,lead
R6224 T22466 T22465 prep of,loss
R6225 T22467 T22466 pobj Apc,of
R6226 T22468 T22451 aux would,lead
R6227 T22469 T22451 advmod inevitably,lead
R6228 T22470 T22451 prep to,lead
R6229 T22471 T22472 amod altered,expression
R6230 T22472 T22470 pobj expression,to
R6231 T22473 T22472 prep of,expression
R6232 T22474 T22475 compound β,catenin
R6233 T22475 T22473 pobj catenin,of
R6234 T22476 T22475 punct -,catenin
R6235 T22477 T22451 prep in,lead
R6236 T22478 T22479 amod ectodermal,cells
R6237 T22479 T22477 pobj cells,in
R6238 T22480 T22451 prep during,lead
R6239 T22481 T22482 det the,formation
R6240 T22482 T22480 pobj formation,during
R6241 T22483 T22484 compound hair,placode
R6242 T22484 T22482 compound placode,formation
R6243 T22485 T22451 punct ", ",lead
R6244 T22486 T22451 advcl giving,lead
R6245 T22487 T22486 dobj rise,giving
R6246 T22488 T22486 prep to,giving
R6247 T22489 T22490 amod aberrant,growth
R6248 T22490 T22488 pobj growth,to
R6249 T22491 T22490 amod follicular,growth
R6250 T22492 T22486 prep throughout,giving
R6251 T22493 T22494 det the,epidermis
R6252 T22494 T22492 pobj epidermis,throughout
R6253 T22495 T22494 amod embryonic,epidermis
R6254 T22496 T22494 punct ", ",epidermis
R6255 T22497 T22494 prep including,epidermis
R6256 T22498 T22499 det the,footpads
R6257 T22499 T22497 pobj footpads,including
R6258 T22500 T22499 punct ", ",footpads
R6259 T22501 T22502 advmod where,hairless
R6260 T22502 T22499 relcl hairless,footpads
R6261 T22503 T22502 advmod normally,hairless
R6262 T22504 T22505 punct (,5B
R6263 T22505 T22451 parataxis 5B,lead
R6264 T22506 T22505 compound Figure,5B
R6265 T22507 T22505 punct ", ",5B
R6266 T22508 T22505 conj 5D,5B
R6267 T22509 T22508 punct ", ",5D
R6268 T22510 T22508 conj 5F,5D
R6269 T22511 T22510 punct ", ",5F
R6270 T22512 T22510 cc and,5F
R6271 T22513 T22510 conj 5H,5F
R6272 T22514 T22505 punct ),5B
R6273 T22515 T22451 punct .,lead
R6274 T22517 T22518 prep Of,are
R6275 T22519 T22517 pobj interest,Of
R6276 T22520 T22521 det the,similarities
R6277 T22521 T22518 nsubj similarities,are
R6278 T22522 T22521 amod phenotypic,similarities
R6279 T22523 T22521 cc and,similarities
R6280 T22524 T22521 conj differences,similarities
R6281 T22525 T22521 prep between,similarities
R6282 T22526 T22527 poss our,mice
R6283 T22527 T22525 pobj mice,between
R6284 T22528 T22527 nmod KA,mice
R6285 T22529 T22527 amod mutant,mice
R6286 T22530 T22527 cc and,mice
R6287 T22531 T22532 det the,mice
R6288 T22532 T22527 conj mice,mice
R6289 T22533 T22534 advmod previously,described
R6290 T22534 T22532 amod described,mice
R6291 T22535 T22536 nmod K14,ΔN87βcat
R6292 T22536 T22532 nmod ΔN87βcat,mice
R6293 T22537 T22536 punct -,ΔN87βcat
R6294 T22538 T22532 amod transgenic,mice
R6295 T22539 T22532 acl expressing,mice
R6296 T22540 T22541 amod stable,catenin
R6297 T22541 T22539 dobj catenin,expressing
R6298 T22542 T22541 compound β,catenin
R6299 T22543 T22541 punct -,catenin
R6300 T22544 T22539 prep under,expressing
R6301 T22545 T22546 det the,control
R6302 T22546 T22544 pobj control,under
R6303 T22547 T22546 prep of,control
R6304 T22548 T22549 compound K14,promoter
R6305 T22549 T22547 pobj promoter,of
R6306 T22550 T22551 punct [,25
R6307 T22551 T22549 parataxis 25,promoter
R6308 T22552 T22551 punct ],25
R6309 T22553 T22549 cc and,promoter
R6310 T22554 T22555 nmod K14,Lef1
R6311 T22555 T22557 nmod Lef1,mice
R6312 T22556 T22555 punct -,Lef1
R6313 T22557 T22549 conj mice,promoter
R6314 T22558 T22555 amod transgenic,Lef1
R6315 T22559 T22560 punct [,27
R6316 T22560 T22557 parataxis 27,mice
R6317 T22561 T22560 punct ],27
R6318 T22562 T22518 punct .,are
R6319 T22564 T22565 advmod Surprisingly,shared
R6320 T22566 T22565 punct ", ",shared
R6321 T22567 T22568 poss our,mice
R6322 T22568 T22565 nsubj mice,shared
R6323 T22569 T22568 amod mutant,mice
R6324 T22570 T22571 amod more,similarities
R6325 T22571 T22565 dobj similarities,shared
R6326 T22572 T22565 prep with,shared
R6327 T22573 T22574 det the,mice
R6328 T22574 T22572 pobj mice,with
R6329 T22575 T22576 compound K14,Lef1
R6330 T22576 T22574 compound Lef1,mice
R6331 T22577 T22576 punct -,Lef1
R6332 T22578 T22565 prep than,shared
R6333 T22579 T22580 det the,mice
R6334 T22580 T22578 pobj mice,than
R6335 T22581 T22582 nmod K14,ΔN87βcat
R6336 T22582 T22580 nmod ΔN87βcat,mice
R6337 T22583 T22582 punct -,ΔN87βcat
R6338 T22584 T22580 amod transgenic,mice
R6339 T22585 T22565 punct .,shared
R6340 T22587 T22588 prep For,displayed
R6341 T22589 T22587 pobj example,For
R6342 T22590 T22588 punct ", ",displayed
R6343 T22591 T22592 det the,mice
R6344 T22592 T22588 nsubj mice,displayed
R6345 T22593 T22592 nmod KA,mice
R6346 T22594 T22592 amod mutant,mice
R6347 T22595 T22596 det the,whiskers
R6348 T22596 T22588 dobj whiskers,displayed
R6349 T22597 T22596 amod disoriented,whiskers
R6350 T22598 T22597 cc and,disoriented
R6351 T22599 T22597 conj short,disoriented
R6352 T22600 T22596 punct ", ",whiskers
R6353 T22601 T22596 amod curly,whiskers
R6354 T22602 T22596 acl seen,whiskers
R6355 T22603 T22602 prep in,seen
R6356 T22604 T22605 compound K14,Lef1but
R6357 T22605 T22603 pobj Lef1but,in
R6358 T22606 T22605 punct -,Lef1but
R6359 T22607 T22603 neg not,in
R6360 T22608 T22603 prep in,in
R6361 T22609 T22610 nmod K14,ΔN87βcat
R6362 T22610 T22612 nmod ΔN87βcat,mice
R6363 T22611 T22610 punct -,ΔN87βcat
R6364 T22612 T22608 pobj mice,in
R6365 T22613 T22612 amod transgenic,mice
R6366 T22614 T22588 punct .,displayed
R6367 T22616 T22617 prep In,displayed
R6368 T22618 T22616 pobj addition,In
R6369 T22619 T22617 punct ", ",displayed
R6370 T22620 T22621 nmod KA,mice
R6371 T22621 T22617 nsubj mice,displayed
R6372 T22622 T22621 amod mutant,mice
R6373 T22623 T22624 det a,coat
R6374 T22624 T22617 dobj coat,displayed
R6375 T22625 T22624 amod disorganized,coat
R6376 T22626 T22624 compound hair,coat
R6377 T22627 T22624 acl beginning,coat
R6378 T22628 T22627 prep with,beginning
R6379 T22629 T22630 det the,emergence
R6380 T22630 T22628 pobj emergence,with
R6381 T22631 T22630 prep of,emergence
R6382 T22632 T22633 amod neonatal,hairs
R6383 T22633 T22631 pobj hairs,of
R6384 T22634 T22633 punct ", ",hairs
R6385 T22635 T22633 amod similar,hairs
R6386 T22636 T22635 prep to,similar
R6387 T22637 T22636 pobj that,to
R6388 T22638 T22637 acl observed,that
R6389 T22639 T22638 prep in,observed
R6390 T22640 T22641 compound K14,Lef1
R6391 T22641 T22643 compound Lef1,mice
R6392 T22642 T22641 punct -,Lef1
R6393 T22643 T22639 pobj mice,in
R6394 T22644 T22617 punct ", ",displayed
R6395 T22645 T22646 mark whereas,was
R6396 T22646 T22617 advcl was,displayed
R6397 T22647 T22646 prep in,was
R6398 T22648 T22649 compound K14,ΔN87βcat
R6399 T22649 T22651 compound ΔN87βcat,mice
R6400 T22650 T22649 punct -,ΔN87βcat
R6401 T22651 T22647 pobj mice,in
R6402 T22652 T22646 punct ", ",was
R6403 T22653 T22654 amod embryonic,morphogenesis
R6404 T22654 T22646 nsubj morphogenesis,was
R6405 T22655 T22656 compound hair,follicle
R6406 T22656 T22654 compound follicle,morphogenesis
R6407 T22657 T22646 acomp unaffected,was
R6408 T22658 T22646 cc and,was
R6409 T22659 T22660 amod other,changes
R6410 T22660 T22662 nsubj changes,emerged
R6411 T22661 T22660 compound skin,changes
R6412 T22662 T22646 conj emerged,was
R6413 T22663 T22662 advmod only,emerged
R6414 T22664 T22662 advmod postnatally,emerged
R6415 T22665 T22617 punct .,displayed
R6416 T22667 T22668 det The,reason
R6417 T22668 T22669 nsubjpass reason,attributed
R6418 T22670 T22668 prep for,reason
R6419 T22671 T22672 det this,difference
R6420 T22672 T22670 pobj difference,for
R6421 T22673 T22669 aux could,attributed
R6422 T22674 T22669 auxpass be,attributed
R6423 T22675 T22669 prep to,attributed
R6424 T22676 T22675 pobj one,to
R6425 T22677 T22676 cc or,one
R6426 T22678 T22676 conj all,one
R6427 T22679 T22676 prep of,one
R6428 T22680 T22681 nummod three,factors
R6429 T22681 T22679 pobj factors,of
R6430 T22682 T22681 amod possible,factors
R6431 T22683 T22681 amod contributing,factors
R6432 T22684 T22669 punct .,attributed
R6433 T22686 T22687 punct (,1
R6434 T22687 T22688 meta 1,influence
R6435 T22689 T22687 punct ),1
R6436 T22690 T22691 mark Although,known
R6437 T22691 T22688 advcl known,influence
R6438 T22692 T22693 det the,promoter
R6439 T22693 T22691 nsubjpass promoter,known
R6440 T22694 T22693 compound K14,promoter
R6441 T22695 T22693 appos itself,promoter
R6442 T22696 T22691 auxpass is,known
R6443 T22697 T22698 aux to,initiate
R6444 T22698 T22691 xcomp initiate,known
R6445 T22699 T22700 det the,expression
R6446 T22700 T22698 dobj expression,initiate
R6447 T22701 T22698 prep at,initiate
R6448 T22702 T22701 pobj E9.5,at
R6449 T22703 T22691 cc and,known
R6450 T22704 T22691 conj elevated,known
R6451 T22705 T22704 advmod dramatically,elevated
R6452 T22706 T22704 prep by,elevated
R6453 T22707 T22706 pobj E13.5,by
R6454 T22708 T22709 punct –,E14.5
R6455 T22709 T22707 prep E14.5,E13.5
R6456 T22710 T22711 punct [,31
R6457 T22711 T22704 parataxis 31,elevated
R6458 T22712 T22711 nummod 19,31
R6459 T22713 T22711 punct ",",31
R6460 T22714 T22711 punct ],31
R6461 T22715 T22688 punct ", ",influence
R6462 T22716 T22717 amod many,factors
R6463 T22717 T22688 nsubj factors,influence
R6464 T22718 T22688 aux could,influence
R6465 T22719 T22720 det the,expression
R6466 T22720 T22688 dobj expression,influence
R6467 T22721 T22720 prep of,expression
R6468 T22722 T22723 compound promoter,transgene
R6469 T22723 T22725 compound transgene,construct
R6470 T22724 T22723 punct /,transgene
R6471 T22725 T22721 pobj construct,of
R6472 T22726 T22688 prep in,influence
R6473 T22727 T22728 amod transgenic,mice
R6474 T22728 T22726 pobj mice,in
R6475 T22729 T22688 punct .,influence
R6476 T22731 T22732 nsubj One,has
R6477 T22733 T22731 prep of,One
R6478 T22734 T22735 det the,considerations
R6479 T22735 T22733 pobj considerations,of
R6480 T22736 T22737 advmod most,important
R6481 T22737 T22735 amod important,considerations
R6482 T22738 T22739 aux to,do
R6483 T22739 T22732 xcomp do,has
R6484 T22740 T22739 prep with,do
R6485 T22741 T22742 det the,site
R6486 T22742 T22740 pobj site,with
R6487 T22743 T22742 compound integration,site
R6488 T22744 T22742 prep of,site
R6489 T22745 T22746 det the,transgene
R6490 T22746 T22744 pobj transgene,of
R6491 T22747 T22739 prep in,do
R6492 T22748 T22749 det the,genome
R6493 T22749 T22747 pobj genome,in
R6494 T22750 T22749 compound mouse,genome
R6495 T22751 T22732 punct .,has
R6496 T22753 T22754 prep Depending,vary
R6497 T22755 T22753 prep on,Depending
R6498 T22756 T22757 det the,location
R6499 T22757 T22755 pobj location,on
R6500 T22758 T22757 prep of,location
R6501 T22759 T22758 pobj integration,of
R6502 T22760 T22754 punct ", ",vary
R6503 T22761 T22762 det the,activity
R6504 T22762 T22754 nsubj activity,vary
R6505 T22763 T22762 amod transcriptional,activity
R6506 T22764 T22762 prep of,activity
R6507 T22765 T22766 advmod even,transgene
R6508 T22766 T22764 pobj transgene,of
R6509 T22767 T22766 det the,transgene
R6510 T22768 T22766 amod same,transgene
R6511 T22769 T22754 aux could,vary
R6512 T22770 T22754 advmod considerably,vary
R6513 T22771 T22754 punct .,vary
R6514 T22773 T22774 nsubj It,is
R6515 T22775 T22774 acomp possible,is
R6516 T22776 T22777 mark that,be
R6517 T22777 T22774 ccomp be,is
R6518 T22778 T22779 det the,lack
R6519 T22779 T22777 nsubj lack,be
R6520 T22780 T22779 amod apparent,lack
R6521 T22781 T22779 prep of,lack
R6522 T22782 T22783 compound ΔN87βcat,function
R6523 T22783 T22781 pobj function,of
R6524 T22784 T22779 prep in,lack
R6525 T22785 T22784 pobj embryogenesis,in
R6526 T22786 T22777 aux could,be
R6527 T22787 T22777 prep due,be
R6528 T22788 T22787 pcomp to,due
R6529 T22789 T22790 det the,expression
R6530 T22790 T22787 pobj expression,due
R6531 T22791 T22790 amod delayed,expression
R6532 T22792 T22791 cc or,delayed
R6533 T22793 T22791 conj weak,delayed
R6534 T22794 T22790 prep of,expression
R6535 T22795 T22796 det the,transgene
R6536 T22796 T22794 pobj transgene,of
R6537 T22797 T22798 compound K14,ΔN87βcat
R6538 T22798 T22796 compound ΔN87βcat,transgene
R6539 T22799 T22798 punct -,ΔN87βcat
R6540 T22800 T22790 prep compared,expression
R6541 T22801 T22800 prep to,compared
R6542 T22802 T22803 det the,promoter
R6543 T22803 T22801 pobj promoter,to
R6544 T22804 T22803 amod intrinsic,promoter
R6545 T22805 T22774 punct .,is
R6546 T22807 T22808 prep In,seen
R6547 T22809 T22807 pobj contrast,In
R6548 T22810 T22808 punct ", ",seen
R6549 T22811 T22812 npadvmod Cre,mediated
R6550 T22812 T22814 amod mediated,recombination
R6551 T22813 T22812 punct -,mediated
R6552 T22814 T22808 nsubjpass recombination,seen
R6553 T22815 T22808 auxpass is,seen
R6554 T22816 T22808 prep in,seen
R6555 T22817 T22818 compound E13.5,skin
R6556 T22818 T22816 pobj skin,in
R6557 T22819 T22818 prep of,skin
R6558 T22820 T22821 nmod K14,cre
R6559 T22821 T22823 nmod cre,mice
R6560 T22822 T22821 punct -,cre
R6561 T22823 T22819 pobj mice,of
R6562 T22824 T22823 amod transgenic,mice
R6563 T22825 T22823 acl used,mice
R6564 T22826 T22825 prep in,used
R6565 T22827 T22828 det this,study
R6566 T22828 T22826 pobj study,in
R6567 T22829 T22830 punct [,16
R6568 T22830 T22808 parataxis 16,seen
R6569 T22831 T22830 punct ],16
R6570 T22832 T22808 cc and,seen
R6571 T22833 T22834 compound K14,cre
R6572 T22834 T22836 npadvmod cre,mediated
R6573 T22835 T22834 punct -,cre
R6574 T22836 T22838 amod mediated,truncation
R6575 T22837 T22836 punct –,mediated
R6576 T22838 T22839 nsubj truncation,is
R6577 T22839 T22808 conj is,seen
R6578 T22840 T22838 prep of,truncation
R6579 T22841 T22842 det the,gene
R6580 T22842 T22840 pobj gene,of
R6581 T22843 T22842 compound Apc,gene
R6582 T22844 T22839 acomp likely,is
R6583 T22845 T22846 aux to,occurred
R6584 T22846 T22844 xcomp occurred,likely
R6585 T22847 T22846 aux have,occurred
R6586 T22848 T22846 prep by,occurred
R6587 T22849 T22848 pcomp then,by
R6588 T22850 T22846 punct ", ",occurred
R6589 T22851 T22846 prep in,occurred
R6590 T22852 T22851 pobj time,in
R6591 T22853 T22852 prep for,time
R6592 T22854 T22855 det the,wave
R6593 T22855 T22853 pobj wave,for
R6594 T22856 T22855 amod second,wave
R6595 T22857 T22855 prep of,wave
R6596 T22858 T22859 compound hair,follicle
R6597 T22859 T22860 compound follicle,morphgenesis
R6598 T22860 T22857 pobj morphgenesis,of
R6599 T22861 T22808 punct .,seen
R6600 T22863 T22864 punct (,2
R6601 T22864 T22865 meta 2,is
R6602 T22866 T22864 punct ),2
R6603 T22867 T22868 det Another,fact
R6604 T22868 T22865 nsubj fact,is
R6605 T22869 T22868 amod important,fact
R6606 T22870 T22871 mark that,confined
R6607 T22871 T22865 ccomp confined,is
R6608 T22872 T22871 prep in,confined
R6609 T22873 T22874 det the,model
R6610 T22874 T22872 pobj model,in
R6611 T22875 T22874 amod aforementioned,model
R6612 T22876 T22874 amod transgenic,model
R6613 T22877 T22878 det the,overexpression
R6614 T22878 T22871 nsubjpass overexpression,confined
R6615 T22879 T22878 prep of,overexpression
R6616 T22880 T22879 pobj transgene,of
R6617 T22881 T22871 auxpass is,confined
R6618 T22882 T22871 prep to,confined
R6619 T22883 T22884 det the,cells
R6620 T22884 T22882 pobj cells,to
R6621 T22885 T22884 amod basal,cells
R6622 T22886 T22884 prep of,cells
R6623 T22887 T22888 det the,epidermis
R6624 T22888 T22886 pobj epidermis,of
R6625 T22889 T22884 cc and,cells
R6626 T22890 T22891 det the,ORS
R6627 T22891 T22884 conj ORS,cells
R6628 T22892 T22891 prep of,ORS
R6629 T22893 T22894 compound hair,follicles
R6630 T22894 T22892 pobj follicles,of
R6631 T22895 T22884 punct ", ",cells
R6632 T22896 T22897 advmod where,is
R6633 T22897 T22884 relcl is,cells
R6634 T22898 T22899 det the,promoter
R6635 T22899 T22897 nsubj promoter,is
R6636 T22900 T22899 compound K14,promoter
R6637 T22901 T22897 acomp active,is
R6638 T22902 T22865 punct .,is
R6639 T22904 T22905 det The,expression
R6640 T22905 T22906 nsubj expression,is
R6641 T22907 T22905 prep of,expression
R6642 T22908 T22907 pobj transgene,of
R6643 T22909 T22906 advmod hence,is
R6644 T22910 T22906 acomp transient,is
R6645 T22911 T22906 cc and,is
R6646 T22912 T22906 conj stops,is
R6647 T22913 T22914 mark once,differentiate
R6648 T22914 T22912 advcl differentiate,stops
R6649 T22915 T22916 npadvmod K14,expressing
R6650 T22916 T22918 amod expressing,cells
R6651 T22917 T22916 punct -,expressing
R6652 T22918 T22914 nsubj cells,differentiate
R6653 T22919 T22914 advmod terminally,differentiate
R6654 T22920 T22906 punct .,is
R6655 T22922 T22923 prep In,result
R6656 T22924 T22922 pobj contrast,In
R6657 T22925 T22923 punct ", ",result
R6658 T22926 T22923 prep in,result
R6659 T22927 T22928 poss our,model
R6660 T22928 T22926 pobj model,in
R6661 T22929 T22923 punct ", ",result
R6662 T22930 T22931 compound K14,cre
R6663 T22931 T22933 npadvmod cre,mediated
R6664 T22932 T22931 punct -,cre
R6665 T22933 T22935 amod mediated,deletion
R6666 T22934 T22933 punct –,mediated
R6667 T22935 T22923 nsubj deletion,result
R6668 T22936 T22935 prep of,deletion
R6669 T22937 T22936 pobj Apc,of
R6670 T22938 T22923 aux would,result
R6671 T22939 T22923 prep in,result
R6672 T22940 T22941 compound Apc,mutation
R6673 T22941 T22939 pobj mutation,in
R6674 T22942 T22943 preconj not,in
R6675 T22943 T22923 prep in,result
R6676 T22944 T22942 advmod only,not
R6677 T22945 T22946 nmod K14,cells
R6678 T22946 T22943 pobj cells,in
R6679 T22947 T22946 nmod promoter,cells
R6680 T22948 T22946 amod active,cells
R6681 T22949 T22923 punct ", ",result
R6682 T22950 T22923 cc but,result
R6683 T22951 T22923 conj remain,result
R6684 T22952 T22951 advmod so,remain
R6685 T22953 T22951 prep in,remain
R6686 T22954 T22955 det all,layers
R6687 T22955 T22953 pobj layers,in
R6688 T22956 T22955 compound cell,layers
R6689 T22957 T22958 dep that,derived
R6690 T22958 T22955 relcl derived,layers
R6691 T22959 T22958 prep from,derived
R6692 T22960 T22961 det the,progenitors
R6693 T22961 T22959 pobj progenitors,from
R6694 T22962 T22963 nmod K14,promoter
R6695 T22963 T22961 nmod promoter,progenitors
R6696 T22964 T22961 amod active,progenitors
R6697 T22965 T22923 punct .,result
R6698 T22967 T22968 det These,derivatives
R6699 T22968 T22969 nsubj derivatives,include
R6700 T22970 T22971 det the,epidermis
R6701 T22971 T22969 dobj epidermis,include
R6702 T22972 T22971 amod suprabasal,epidermis
R6703 T22973 T22971 cc and,epidermis
R6704 T22974 T22975 det the,epithelium
R6705 T22975 T22971 conj epithelium,epidermis
R6706 T22976 T22975 amod entire,epithelium
R6707 T22977 T22975 prep of,epithelium
R6708 T22978 T22979 det the,follicle
R6709 T22979 T22977 pobj follicle,of
R6710 T22980 T22979 compound hair,follicle
R6711 T22981 T22969 punct .,include
R6712 T22983 T22984 nsubj Stabilization,account
R6713 T22985 T22983 prep of,Stabilization
R6714 T22986 T22987 compound β,catenin
R6715 T22987 T22985 pobj catenin,of
R6716 T22988 T22987 punct -,catenin
R6717 T22989 T22983 prep in,Stabilization
R6718 T22990 T22991 det a,population
R6719 T22991 T22989 pobj population,in
R6720 T22992 T22991 amod broader,population
R6721 T22993 T22991 prep of,population
R6722 T22994 T22993 pobj cells,of
R6723 T22995 T22984 aux could,account
R6724 T22996 T22984 prep for,account
R6725 T22997 T22996 pobj some,for
R6726 T22998 T22997 prep of,some
R6727 T22999 T23000 det the,differences
R6728 T23000 T22998 pobj differences,of
R6729 T23001 T23000 amod phenotypic,differences
R6730 T23002 T22984 punct .,account
R6731 T23004 T23005 advmod However,detect
R6732 T23006 T23005 punct ", ",detect
R6733 T23007 T23005 nsubj we,detect
R6734 T23008 T23005 aux did,detect
R6735 T23009 T23005 neg not,detect
R6736 T23010 T23011 det any,expression
R6737 T23011 T23005 dobj expression,detect
R6738 T23012 T23011 amod elevated,expression
R6739 T23013 T23014 compound β,catenin
R6740 T23014 T23011 compound catenin,expression
R6741 T23015 T23014 punct -,catenin
R6742 T23016 T23005 prep in,detect
R6743 T23017 T23018 preconj either,cells
R6744 T23018 T23016 pobj cells,in
R6745 T23019 T23020 npadvmod K1,positive
R6746 T23020 T23018 amod positive,cells
R6747 T23021 T23019 punct -,K1
R6748 T23022 T23019 cc or,K1
R6749 T23023 T23019 conj K6,K1
R6750 T23024 T23020 punct -,positive
R6751 T23025 T23018 amod differentiated,cells
R6752 T23026 T23005 prep in,detect
R6753 T23027 T23028 amod postnatal,skin
R6754 T23028 T23026 pobj skin,in
R6755 T23029 T23028 amod mutant,skin
R6756 T23030 T23005 punct .,detect
R6757 T23032 T23033 nsubj This,indicates
R6758 T23034 T23035 mark that,take
R6759 T23035 T23033 ccomp take,indicates
R6760 T23036 T23035 prep despite,take
R6761 T23037 T23038 det the,absence
R6762 T23038 T23036 pobj absence,despite
R6763 T23039 T23038 prep of,absence
R6764 T23040 T23039 pobj Apc,of
R6765 T23041 T23038 cc and,absence
R6766 T23042 T23043 amod potential,stabilization
R6767 T23043 T23038 conj stabilization,absence
R6768 T23044 T23043 prep of,stabilization
R6769 T23045 T23046 compound β,catenin
R6770 T23046 T23044 pobj catenin,of
R6771 T23047 T23046 punct -,catenin
R6772 T23048 T23038 prep in,absence
R6773 T23049 T23048 pobj derivatives,in
R6774 T23050 T23049 prep of,derivatives
R6775 T23051 T23052 npadvmod K14,expressing
R6776 T23052 T23054 amod expressing,progenitors
R6777 T23053 T23052 punct -,expressing
R6778 T23054 T23050 pobj progenitors,of
R6779 T23055 T23035 punct ", ",take
R6780 T23056 T23057 amod elevated,expression
R6781 T23057 T23035 nsubj expression,take
R6782 T23058 T23059 compound β,catenin
R6783 T23059 T23057 compound catenin,expression
R6784 T23060 T23059 punct -,catenin
R6785 T23061 T23057 punct ", ",expression
R6786 T23062 T23057 cc and,expression
R6787 T23063 T23064 amod subsequent,determination
R6788 T23064 T23057 conj determination,expression
R6789 T23065 T23066 compound cell,fate
R6790 T23066 T23064 compound fate,determination
R6791 T23067 T23035 aux may,take
R6792 T23068 T23035 advmod only,take
R6793 T23069 T23035 dobj place,take
R6794 T23070 T23035 prep in,take
R6795 T23071 T23072 amod basal,cells
R6796 T23072 T23070 pobj cells,in
R6797 T23073 T23033 punct .,indicates
R6798 T23075 T23076 punct (,3
R6799 T23076 T23077 meta 3,exclude
R6800 T23078 T23076 punct ),3
R6801 T23079 T23077 nsubj We,exclude
R6802 T23080 T23077 aux can,exclude
R6803 T23081 T23077 neg not,exclude
R6804 T23082 T23083 det the,possibility
R6805 T23083 T23077 dobj possibility,exclude
R6806 T23084 T23085 mark that,contributed
R6807 T23085 T23083 acl contributed,possibility
R6808 T23086 T23085 prep given,contributed
R6809 T23087 T23088 det the,properties
R6810 T23088 T23086 pobj properties,given
R6811 T23089 T23088 amod multifunctional,properties
R6812 T23090 T23088 prep of,properties
R6813 T23091 T23090 pobj Apc,of
R6814 T23092 T23085 punct ", ",contributed
R6815 T23093 T23085 nsubj disruption,contributed
R6816 T23094 T23093 prep of,disruption
R6817 T23095 T23096 poss its,functions
R6818 T23096 T23094 pobj functions,of
R6819 T23097 T23096 amod other,functions
R6820 T23098 T23097 prep than,other
R6821 T23099 T23100 advmod down,regulation
R6822 T23100 T23098 pobj regulation,than
R6823 T23101 T23100 punct -,regulation
R6824 T23102 T23100 prep of,regulation
R6825 T23103 T23104 compound β,catenin
R6826 T23104 T23102 pobj catenin,of
R6827 T23105 T23104 punct -,catenin
R6828 T23106 T23085 aux may,contributed
R6829 T23107 T23085 advmod also,contributed
R6830 T23108 T23085 aux have,contributed
R6831 T23109 T23085 prep to,contributed
R6832 T23110 T23111 det the,phenotype
R6833 T23111 T23109 pobj phenotype,to
R6834 T23112 T23111 amod observed,phenotype
R6835 T23113 T23111 amod overt,phenotype
R6836 T23114 T23077 punct .,exclude
R6837 T23116 T23117 mark While,were
R6838 T23117 T23124 advcl were,were
R6839 T23118 T23119 det some,features
R6840 T23119 T23117 nsubj features,were
R6841 T23120 T23119 prep of,features
R6842 T23121 T23122 poss our,mice
R6843 T23122 T23120 pobj mice,of
R6844 T23123 T23122 amod mutant,mice
R6845 T23125 T23117 acomp similar,were
R6846 T23126 T23125 prep to,similar
R6847 T23127 T23128 det these,mice
R6848 T23128 T23126 pobj mice,to
R6849 T23129 T23128 amod transgenic,mice
R6850 T23130 T23124 punct ", ",were
R6851 T23131 T23132 amod other,aspects
R6852 T23132 T23124 nsubj aspects,were
R6853 T23133 T23132 amod phenotypic,aspects
R6854 T23134 T23135 advmod largely,distinct
R6855 T23135 T23124 acomp distinct,were
R6856 T23136 T23124 punct .,were
R6857 T23138 T23139 prep In,caused
R6858 T23140 T23138 pobj addition,In
R6859 T23141 T23140 prep to,addition
R6860 T23142 T23143 amod aberrant,morphogenesis
R6861 T23143 T23141 pobj morphogenesis,to
R6862 T23144 T23145 compound hair,follicle
R6863 T23145 T23143 compound follicle,morphogenesis
R6864 T23146 T23139 punct ", ",caused
R6865 T23147 T23148 npadvmod K14,driven
R6866 T23148 T23150 amod driven,loss
R6867 T23149 T23148 punct -,driven
R6868 T23150 T23139 nsubj loss,caused
R6869 T23151 T23150 prep of,loss
R6870 T23152 T23151 pobj Apc,of
R6871 T23153 T23139 dobj formation,caused
R6872 T23154 T23153 prep of,formation
R6873 T23155 T23156 amod multiple,buds
R6874 T23156 T23154 pobj buds,of
R6875 T23157 T23156 compound tooth,buds
R6876 T23158 T23159 dep that,known
R6877 T23159 T23156 relcl known,buds
R6878 T23160 T23159 punct ", ",known
R6879 T23161 T23159 prep like,known
R6880 T23162 T23163 compound hair,follicles
R6881 T23163 T23161 pobj follicles,like
R6882 T23164 T23159 punct ", ",known
R6883 T23165 T23159 auxpass were,known
R6884 T23166 T23167 aux to,develop
R6885 T23167 T23159 xcomp develop,known
R6886 T23168 T23167 prep through,develop
R6887 T23169 T23170 amod inductive,interactions
R6888 T23170 T23168 pobj interactions,through
R6889 T23171 T23170 prep between,interactions
R6890 T23172 T23173 det the,epithelium
R6891 T23173 T23171 pobj epithelium,between
R6892 T23174 T23173 cc and,epithelium
R6893 T23175 T23173 conj mesenchyme,epithelium
R6894 T23176 T23139 punct .,caused
R6895 T23178 T23179 det This,observation
R6896 T23179 T23180 nsubj observation,was
R6897 T23181 T23180 acomp similar,was
R6898 T23182 T23181 prep to,similar
R6899 T23183 T23184 det the,buds
R6900 T23184 T23182 pobj buds,to
R6901 T23185 T23184 amod ectopic,buds
R6902 T23186 T23184 compound tooth,buds
R6903 T23187 T23184 acl found,buds
R6904 T23188 T23187 prep in,found
R6905 T23189 T23188 pobj animals,in
R6906 T23190 T23189 acl misexpressing,animals
R6907 T23191 T23190 dobj Lef1,misexpressing
R6908 T23192 T23193 punct [,27
R6909 T23193 T23187 parataxis 27,found
R6910 T23194 T23193 punct ],27
R6911 T23195 T23181 punct ", ",similar
R6912 T23196 T23181 cc but,similar
R6913 T23197 T23198 advmod more,severe
R6914 T23198 T23181 conj severe,similar
R6915 T23199 T23180 cc and,was
R6916 T23200 T23180 conj was,was
R6917 T23201 T23200 advmod also,was
R6918 T23202 T23200 acomp present,was
R6919 T23203 T23200 prep at,was
R6920 T23204 T23203 pobj birth,at
R6921 T23205 T23200 punct ", ",was
R6922 T23206 T23200 advcl indicating,was
R6923 T23207 T23208 det the,effect
R6924 T23208 T23206 dobj effect,indicating
R6925 T23209 T23208 prep of,effect
R6926 T23210 T23211 compound Apc,loss
R6927 T23211 T23209 pobj loss,of
R6928 T23212 T23211 prep during,loss
R6929 T23213 T23214 det the,initiation
R6930 T23214 T23212 pobj initiation,during
R6931 T23215 T23214 prep of,initiation
R6932 T23216 T23217 amod embryonic,development
R6933 T23217 T23215 pobj development,of
R6934 T23218 T23217 compound tooth,development
R6935 T23219 T23208 punct ", ",effect
R6936 T23220 T23221 dep which,was
R6937 T23221 T23208 relcl was,effect
R6938 T23222 T23221 acomp evident,was
R6939 T23223 T23221 prep by,was
R6940 T23224 T23225 amod aberrant,expression
R6941 T23225 T23223 pobj expression,by
R6942 T23226 T23225 compound Shh,expression
R6943 T23227 T23225 prep in,expression
R6944 T23228 T23229 nmod E15.5,epithelium
R6945 T23229 T23227 pobj epithelium,in
R6946 T23230 T23229 amod embryonic,epithelium
R6947 T23231 T23229 amod oral,epithelium
R6948 T23232 T23233 punct (,data
R6949 T23233 T23206 meta data,indicating
R6950 T23234 T23233 amod unpublished,data
R6951 T23235 T23233 punct ),data
R6952 T23236 T23180 punct .,was
R6953 T23238 T23239 nsubjpass It,noted
R6954 T23240 T23239 aux should,noted
R6955 T23241 T23239 auxpass be,noted
R6956 T23242 T23243 mark that,broke
R6957 T23243 T23239 ccomp broke,noted
R6958 T23244 T23245 mark although,were
R6959 T23245 T23243 advcl were,broke
R6960 T23246 T23247 amod multiple,buds
R6961 T23247 T23245 nsubj buds,were
R6962 T23248 T23247 compound tooth,buds
R6963 T23249 T23250 advmod histologically,visible
R6964 T23250 T23245 acomp visible,were
R6965 T23251 T23252 punct (,4O
R6966 T23252 T23245 parataxis 4O,were
R6967 T23253 T23252 compound Figure,4O
R6968 T23254 T23252 cc and,4O
R6969 T23255 T23252 conj 4P,4O
R6970 T23256 T23252 punct ),4O
R6971 T23257 T23243 punct ", ",broke
R6972 T23258 T23259 det these,teeth
R6973 T23259 T23243 nsubj teeth,broke
R6974 T23260 T23243 neg never,broke
R6975 T23261 T23243 prt out,broke
R6976 T23262 T23243 cc and,broke
R6977 T23263 T23264 det the,mice
R6978 T23264 T23267 nsubj mice,appeared
R6979 T23265 T23264 nmod KA,mice
R6980 T23266 T23264 amod mutant,mice
R6981 T23267 T23243 conj appeared,broke
R6982 T23268 T23267 oprd toothless,appeared
R6983 T23375 T23373 pobj consequence,as
R6984 T23376 T23375 prep of,consequence
R6985 T23377 T23378 amod poor,nutrition
R6986 T23378 T23376 pobj nutrition,of
R6987 T23379 T23378 acl caused,nutrition
R6988 T23380 T23379 agent by,caused
R6989 T23381 T23382 det the,absence
R6990 T23269 T23239 punct .,noted
R6991 T23382 T23380 pobj absence,by
R6992 T23383 T23382 prep of,absence
R6993 T23271 T23272 det This,defect
R6994 T23384 T23383 pobj teeth,of
R6995 T23385 T23365 punct .,reduced
R6996 T23272 T23276 nsubj defect,is
R6997 T23273 T23272 amod unusual,defect
R6998 T23387 T23388 mark Since,started
R6999 T23274 T23272 amod severe,defect
R7000 T23275 T23272 compound tooth,defect
R7001 T23388 T23395 advcl started,be
R7002 T23277 T23276 acomp unique,is
R7003 T23278 T23277 prep to,unique
R7004 T23279 T23280 det these,mice
R7005 T23389 T23390 det the,loss
R7006 T23280 T23278 pobj mice,to
R7007 T23281 T23280 amod mutant,mice
R7008 T23390 T23388 nsubj loss,started
R7009 T23282 T23276 punct .,is
R7010 T23284 T23285 prep In,was
R7011 T23391 T23390 compound weight,loss
R7012 T23392 T23390 prep in,loss
R7013 T23286 T23284 pobj addition,In
R7014 T23287 T23285 punct ", ",was
R7015 T23393 T23394 compound KA,mutants
R7016 T23288 T23285 nsubj neither,was
R7017 T23289 T23288 prep of,neither
R7018 T23290 T23291 det the,mice
R7019 T23394 T23392 pobj mutants,in
R7020 T23291 T23289 pobj mice,of
R7021 T23292 T23291 nummod two,mice
R7022 T23293 T23291 amod transgenic,mice
R7023 T23396 T23388 prep from,started
R7024 T23294 T23295 advmod postnatally,lethal
R7025 T23295 T23285 acomp lethal,was
R7026 T23296 T23285 prep as,was
R7027 T23297 T23296 prep in,as
R7028 T23298 T23299 det the,mice
R7029 T23299 T23297 pobj mice,in
R7030 T23397 T23396 pobj P8,from
R7031 T23300 T23299 nmod KA,mice
R7032 T23301 T23299 amod mutant,mice
R7033 T23302 T23285 punct .,was
R7034 T23398 T23399 punct –,P10
R7035 T23399 T23397 prep P10,P8
R7036 T23304 T23305 nsubj We,find
R7037 T23306 T23305 aux did,find
R7038 T23307 T23305 neg not,find
R7039 T23308 T23309 det any,abnormalities
R7040 T23400 T23401 mark while,nursed
R7041 T23309 T23305 dobj abnormalities,find
R7042 T23310 T23309 amod obvious,abnormalities
R7043 T23311 T23309 amod histopathological,abnormalities
R7044 T23312 T23309 prep in,abnormalities
R7045 T23401 T23388 advcl nursed,started
R7046 T23313 T23314 det the,organs
R7047 T23314 T23312 pobj organs,in
R7048 T23315 T23314 amod internal,organs
R7049 T23402 T23401 nsubjpass pups,nursed
R7050 T23316 T23314 prep of,organs
R7051 T23317 T23318 compound KA,mice
R7052 T23318 T23316 pobj mice,of
R7053 T23403 T23401 auxpass were,nursed
R7054 T23319 T23320 dep that,contribute
R7055 T23320 T23309 relcl contribute,abnormalities
R7056 T23321 T23320 aux could,contribute
R7057 T23404 T23401 advmod still,nursed
R7058 T23322 T23320 prep to,contribute
R7059 T23323 T23324 det the,lethality
R7060 T23405 T23401 agent by,nursed
R7061 T23324 T23322 pobj lethality,to
R7062 T23325 T23305 punct .,find
R7063 T23406 T23407 poss their,mothers
R7064 T23327 T23328 advmod However,indicates
R7065 T23407 T23405 pobj mothers,by
R7066 T23329 T23328 punct ", ",indicates
R7067 T23330 T23331 det the,fact
R7068 T23331 T23328 nsubj fact,indicates
R7069 T23408 T23395 punct ", ",be
R7070 T23332 T23333 mark that,had
R7071 T23333 T23331 acl had,fact
R7072 T23334 T23335 predet all,mutants
R7073 T23409 T23395 nsubj starvation,be
R7074 T23335 T23333 nsubj mutants,had
R7075 T23336 T23335 det the,mutants
R7076 T23337 T23338 amod lower,weight
R7077 T23338 T23333 dobj weight,had
R7078 T23339 T23340 punct (,2F
R7079 T23340 T23338 parataxis 2F,weight
R7080 T23410 T23409 prep due,starvation
R7081 T23341 T23340 compound Figure,2F
R7082 T23342 T23340 punct ),2F
R7083 T23343 T23338 prep with,weight
R7084 T23411 T23410 pcomp to,due
R7085 T23344 T23345 advmod hardly,evidence
R7086 T23345 T23343 pobj evidence,with
R7087 T23412 T23410 pobj lack,due
R7088 T23346 T23345 det any,evidence
R7089 T23347 T23345 prep of,evidence
R7090 T23348 T23349 amod solid,food
R7091 T23349 T23347 pobj food,of
R7092 T23413 T23412 prep of,lack
R7093 T23350 T23345 prep in,evidence
R7094 T23351 T23352 poss their,stomach
R7095 T23352 T23350 pobj stomach,in
R7096 T23414 T23413 pobj teeth,of
R7097 T23353 T23354 mark that,died
R7098 T23354 T23328 ccomp died,indicates
R7099 T23355 T23356 det the,mutants
R7100 T23415 T23395 aux can,be
R7101 T23356 T23354 nsubj mutants,died
R7102 T23357 T23354 aux might,died
R7103 T23358 T23354 aux have,died
R7104 T23416 T23395 neg not,be
R7105 T23359 T23354 prep of,died
R7106 T23360 T23359 pobj starvation,of
R7107 T23361 T23328 punct .,indicates
R7108 T23417 T23418 det the,cause
R7109 T23418 T23395 attr cause,be
R7110 T23363 T23364 amod Dermal,fat
R7111 T23419 T23418 amod sole,cause
R7112 T23364 T23365 nsubjpass fat,reduced
R7113 T23420 T23418 prep of,cause
R7114 T23366 T23365 auxpass was,reduced
R7115 T23367 T23365 prep in,reduced
R7116 T23421 T23420 pobj death,of
R7117 T23368 T23369 det the,skin
R7118 T23369 T23367 pobj skin,in
R7119 T23370 T23369 amod mutant,skin
R7120 T23422 T23395 punct ", ",be
R7121 T23371 T23365 punct ", ",reduced
R7122 T23372 T23373 advmod possibly,as
R7123 T23423 T23395 cc but,be
R7124 T23373 T23365 prep as,reduced
R7125 T23374 T23375 det a,consequence
R7126 T23424 T23395 conj is,be
R7127 T23425 T23424 acomp likely,is
R7128 T23426 T23427 aux to,be
R7129 T23427 T23425 xcomp be,likely
R7130 T23428 T23429 det a,factor
R7131 T23481 T23482 compound bud,formation
R7132 T23482 T23479 pobj formation,of
R7133 T23483 T23484 amod proper,development
R7134 T23429 T23427 attr factor,be
R7135 T23484 T23473 dobj development,allows
R7136 T23485 T23484 prep of,development
R7137 T23486 T23485 pobj teeth,of
R7138 T23430 T23429 amod contributing,factor
R7139 T23487 T23488 mark for,have
R7140 T23488 T23473 advcl have,allows
R7141 T23489 T23488 nsubj mice,have
R7142 T23431 T23395 punct .,be
R7143 T23490 T23488 aux to,have
R7144 T23491 T23492 det a,diet
R7145 T23433 T23434 nsubjpass Absence,observed
R7146 T23492 T23488 dobj diet,have
R7147 T23493 T23492 amod healthy,diet
R7148 T23494 T23492 cc and,diet
R7149 T23435 T23433 prep of,Absence
R7150 T23495 T23496 amod normal,life
R7151 T23496 T23492 conj life,diet
R7152 T23497 T23473 punct .,allows
R7153 T23499 T23500 amod Mechanistic,studies
R7154 T23436 T23435 pobj teeth,of
R7155 T23500 T23501 nsubj studies,are
R7156 T23437 T23436 cc and,teeth
R7157 T23502 T23503 aux to,understand
R7158 T23503 T23500 advcl understand,studies
R7159 T23504 T23505 advmod how,leads
R7160 T23438 T23439 amod mammary,glands
R7161 T23505 T23503 ccomp leads,understand
R7162 T23506 T23507 amod increased,levels
R7163 T23507 T23505 nsubj levels,leads
R7164 T23439 T23436 conj glands,teeth
R7165 T23508 T23507 prep of,levels
R7166 T23509 T23510 compound β,catenin
R7167 T23440 T23434 aux have,observed
R7168 T23510 T23508 pobj catenin,of
R7169 T23511 T23510 punct -,catenin
R7170 T23512 T23505 prep to,leads
R7171 T23441 T23434 auxpass been,observed
R7172 T23513 T23514 amod altered,phenotypes
R7173 T23514 T23512 pobj phenotypes,to
R7174 T23515 T23514 nmod skin,phenotypes
R7175 T23442 T23434 prep in,observed
R7176 T23516 T23515 cc and,skin
R7177 T23517 T23515 conj tooth,skin
R7178 T23518 T23501 prep under,are
R7179 T23443 T23442 pobj mice,in
R7180 T23519 T23518 pobj way,under
R7181 T23520 T23501 punct .,are
R7182 T23444 T23443 amod deficient,mice
R7183 T23445 T23444 prep in,deficient
R7184 T23446 T23445 pobj Lef1,in
R7185 T23447 T23444 cc and,deficient
R7186 T23448 T23449 advmod ectopically,expressing
R7187 T23449 T23444 conj expressing,deficient
R7188 T23450 T23449 dobj Dkk1,expressing
R7189 T23451 T23452 punct [,30
R7190 T23452 T23434 parataxis 30,observed
R7191 T23453 T23452 nummod 29,30
R7192 T23454 T23452 punct ",",30
R7193 T23455 T23452 punct ],30
R7194 T23456 T23434 cc but,observed
R7195 T23457 T23458 poss their,absence
R7196 T23458 T23459 nsubj absence,was
R7197 T23459 T23434 conj was,observed
R7198 T23460 T23459 prep due,was
R7199 T23461 T23460 pcomp to,due
R7200 T23462 T23463 det the,block
R7201 T23463 T23460 pobj block,due
R7202 T23464 T23463 prep in,block
R7203 T23465 T23464 pobj development,in
R7204 T23466 T23463 prep before,block
R7205 T23467 T23468 det the,stage
R7206 T23468 T23466 pobj stage,before
R7207 T23469 T23468 compound bud,stage
R7208 T23470 T23459 punct .,was
R7209 T23472 T23473 advmod Hence,allows
R7210 T23474 T23473 punct ", ",allows
R7211 T23475 T23476 preconj neither,loss
R7212 T23476 T23473 nsubj loss,allows
R7213 T23477 T23476 cc nor,loss
R7214 T23478 T23476 conj excess,loss
R7215 T23479 T23476 prep of,loss
R7216 T23480 T23481 amod tooth,bud
R7221 T25418 T25417 cc and,Apc
R7222 T25419 T25420 compound Thymus,Organogenesis
R7223 T25420 T25417 conj Organogenesis,Apc
R7224 T25422 T25423 prep In,observed
R7225 T25424 T25425 det this,study
R7226 T25425 T25422 pobj study,In
R7227 T25426 T25423 punct ", ",observed
R7228 T25427 T25423 nsubj we,observed
R7229 T25428 T25429 mark that,resulted
R7230 T25429 T25423 ccomp resulted,observed
R7231 T25430 T25431 npadvmod K14,driven
R7232 T25431 T25433 amod driven,loss
R7233 T25432 T25431 punct -,driven
R7234 T25433 T25429 nsubj loss,resulted
R7235 T25434 T25433 prep of,loss
R7236 T25435 T25434 pobj Apc,of
R7237 T25436 T25429 prep in,resulted
R7238 T25437 T25438 det a,thymus
R7239 T25438 T25436 pobj thymus,in
R7240 T25439 T25438 amod small,thymus
R7241 T25440 T25438 prep with,thymus
R7242 T25441 T25442 amod severe,metaplasia
R7243 T25442 T25440 pobj metaplasia,with
R7244 T25443 T25442 amod squamous,metaplasia
R7245 T25444 T25442 acl leading,metaplasia
R7246 T25445 T25444 prep to,leading
R7247 T25446 T25447 det the,formation
R7248 T25447 T25445 pobj formation,to
R7249 T25448 T25447 prep of,formation
R7250 T25449 T25450 amod numerous,pyogranuloma
R7251 T25450 T25448 pobj pyogranuloma,of
R7252 T25451 T25447 cc and,formation
R7253 T25452 T25447 conj loss,formation
R7254 T25453 T25452 prep of,loss
R7255 T25454 T25455 amod proper,structure
R7256 T25455 T25453 pobj structure,of
R7257 T25456 T25455 compound meshwork,structure
R7258 T25457 T25455 prep for,structure
R7259 T25458 T25459 compound thymocyte,maturation
R7260 T25459 T25457 pobj maturation,for
R7261 T25460 T25429 punct ", ",resulted
R7262 T25461 T25429 advcl rendering,resulted
R7263 T25462 T25463 det the,mice
R7264 T25463 T25461 dobj mice,rendering
R7265 T25464 T25461 oprd athymic,rendering
R7266 T25465 T25423 punct .,observed
R7267 T25467 T25468 amod Previous,studies
R7268 T25468 T25469 nsubj studies,shown
R7269 T25470 T25469 aux have,shown
R7270 T25471 T25472 mark that,found
R7271 T25472 T25469 ccomp found,shown
R7272 T25473 T25472 prep in,found
R7273 T25474 T25475 amod normal,thymus
R7274 T25475 T25473 pobj thymus,in
R7275 T25476 T25475 amod adult,thymus
R7276 T25477 T25478 compound K14,expression
R7277 T25478 T25472 nsubjpass expression,found
R7278 T25479 T25472 auxpass is,found
R7279 T25480 T25481 advmod together,in
R7280 T25481 T25472 prep in,found
R7281 T25482 T25480 prep with,together
R7282 T25483 T25482 pobj K5,with
R7283 T25484 T25483 prep in,K5
R7284 T25485 T25486 det the,TECs
R7285 T25486 T25484 pobj TECs,in
R7286 T25487 T25486 amod stellate,TECs
R7287 T25488 T25486 amod medullary,TECs
R7288 T25489 T25481 punct ", ",in
R7289 T25490 T25481 cc but,in
R7290 T25491 T25490 neg not,but
R7291 T25492 T25481 pobj association,in
R7292 T25493 T25492 prep with,association
R7293 T25494 T25495 nmod K5,TECs
R7294 T25495 T25493 pobj TECs,with
R7295 T25496 T25494 punct +,K5
R7296 T25497 T25492 prep in,association
R7297 T25498 T25499 det the,cortex
R7298 T25499 T25497 pobj cortex,in
R7299 T25500 T25497 cc or,in
R7300 T25501 T25497 conj at,in
R7301 T25502 T25503 det the,junction
R7302 T25503 T25501 pobj junction,at
R7303 T25504 T25505 amod cortico,medullary
R7304 T25505 T25503 amod medullary,junction
R7305 T25506 T25505 punct -,medullary
R7306 T25507 T25469 punct .,shown
R7307 T25509 T25510 prep In,demonstrated
R7308 T25510 T25516 ccomp demonstrated,are
R7309 T25511 T25509 pobj addition,In
R7310 T25512 T25510 punct ", ",demonstrated
R7311 T25513 T25510 nsubjpass it,demonstrated
R7312 T25514 T25510 aux has,demonstrated
R7313 T25515 T25510 auxpass been,demonstrated
R7314 T25517 T25518 mark that,coexpress
R7315 T25518 T25510 ccomp coexpress,demonstrated
R7316 T25519 T25520 nmod K14,TECs
R7317 T25520 T25518 nsubj TECs,coexpress
R7318 T25521 T25519 punct +,K14
R7319 T25522 T25518 aux do,coexpress
R7320 T25523 T25518 neg not,coexpress
R7321 T25524 T25518 dobj K8,coexpress
R7322 T25525 T25516 punct ;,are
R7323 T25526 T25516 advmod hence,are
R7324 T25527 T25516 punct ", ",are
R7325 T25528 T25516 expl there,are
R7326 T25529 T25530 nummod two,subsets
R7327 T25530 T25516 attr subsets,are
R7328 T25531 T25530 amod distinct,subsets
R7329 T25532 T25530 amod medullary,subsets
R7330 T25533 T25530 punct ", ",subsets
R7331 T25534 T25535 advmod namely,subset
R7332 T25535 T25530 appos subset,subsets
R7333 T25536 T25535 det a,subset
R7334 T25537 T25535 nmod K8,subset
R7335 T25538 T25537 punct −,K8
R7336 T25539 T25535 nmod K14,subset
R7337 T25540 T25539 punct +,K14
R7338 T25541 T25535 amod stellate,subset
R7339 T25542 T25535 cc and,subset
R7340 T25543 T25544 det a,subset
R7341 T25544 T25535 conj subset,subset
R7342 T25545 T25544 nmod K8,subset
R7343 T25546 T25545 punct +,K8
R7344 T25547 T25544 nmod K14,subset
R7345 T25548 T25547 punct −,K14
R7346 T25549 T25544 amod globular,subset
R7347 T25550 T25551 punct [,32
R7348 T25551 T25516 parataxis 32,are
R7349 T25552 T25551 punct ],32
R7350 T25553 T25516 punct .,are
R7351 T25555 T25556 prep In,restricted
R7352 T25557 T25555 pobj agreement,In
R7353 T25558 T25557 prep with,agreement
R7354 T25559 T25560 det the,results
R7355 T25560 T25558 pobj results,with
R7356 T25561 T25560 amod previous,results
R7357 T25562 T25556 punct ", ",restricted
R7358 T25563 T25556 prep in,restricted
R7359 T25564 T25565 nmod P3,thymus
R7360 T25565 T25563 pobj thymus,in
R7361 T25566 T25565 amod normal,thymus
R7362 T25567 T25568 compound K14,expression
R7363 T25568 T25556 nsubjpass expression,restricted
R7364 T25569 T25556 auxpass was,restricted
R7365 T25570 T25556 prep to,restricted
R7366 T25571 T25572 amod stellate,TECs
R7367 T25572 T25570 pobj TECs,to
R7368 T25573 T25572 amod medullary,TECs
R7369 T25574 T25575 punct (,6D
R7370 T25575 T25556 parataxis 6D,restricted
R7371 T25576 T25575 compound Figure,6D
R7372 T25577 T25575 punct ),6D
R7373 T25578 T25556 punct ", ",restricted
R7374 T25579 T25580 mark whereas,found
R7375 T25580 T25556 advcl found,restricted
R7376 T25581 T25582 compound K8,expression
R7377 T25582 T25580 nsubjpass expression,found
R7378 T25583 T25580 auxpass was,found
R7379 T25584 T25580 prep throughout,found
R7380 T25585 T25586 det the,TECs
R7381 T25586 T25584 pobj TECs,throughout
R7382 T25587 T25588 punct (,data
R7383 T25588 T25556 meta data,restricted
R7384 T25589 T25588 amod unpublished,data
R7385 T25590 T25588 punct ),data
R7386 T25591 T25556 punct .,restricted
R7387 T25593 T25594 nsubj We,clarify
R7388 T25595 T25594 aux could,clarify
R7389 T25596 T25594 neg not,clarify
R7390 T25597 T25598 mark whether,coexpressed
R7391 T25598 T25594 ccomp coexpressed,clarify
R7392 T25599 T25600 det these,keratins
R7393 T25600 T25598 nsubjpass keratins,coexpressed
R7394 T25601 T25600 nummod two,keratins
R7395 T25602 T25598 auxpass were,coexpressed
R7396 T25603 T25598 prep in,coexpressed
R7397 T25604 T25605 det the,TECs
R7398 T25605 T25603 pobj TECs,in
R7399 T25606 T25605 amod same,TECs
R7400 T25607 T25598 prep without,coexpressed
R7401 T25608 T25609 compound double,staining
R7402 T25609 T25607 pobj staining,without
R7403 T25610 T25609 punct -,staining
R7404 T25611 T25594 punct .,clarify
R7405 T25613 T25614 expl There,were
R7406 T25615 T25616 amod individual,differences
R7407 T25616 T25614 attr differences,were
R7408 T25617 T25614 prep among,were
R7409 T25618 T25617 pobj mutants,among
R7410 T25619 T25614 cc and,were
R7411 T25620 T25621 nsubjpass these,reflected
R7412 T25621 T25614 conj reflected,were
R7413 T25622 T25621 auxpass were,reflected
R7414 T25623 T25621 advmod prominently,reflected
R7415 T25624 T25621 prep in,reflected
R7416 T25625 T25626 det the,abnormalities
R7417 T25626 T25624 pobj abnormalities,in
R7418 T25627 T25626 amod histological,abnormalities
R7419 T25628 T25626 prep of,abnormalities
R7420 T25629 T25630 det the,thymus
R7421 T25630 T25628 pobj thymus,of
R7422 T25631 T25621 prep at,reflected
R7423 T25632 T25631 pobj P3,at
R7424 T25633 T25614 punct ", ",were
R7425 T25634 T25614 cc but,were
R7426 T25635 T25636 mark as,showed
R7427 T25636 T25642 advcl showed,seem
R7428 T25637 T25638 det the,mutants
R7429 T25638 T25636 nsubj mutants,showed
R7430 T25639 T25638 amod older,mutants
R7431 T25640 T25638 amod surviving,mutants
R7432 T25641 T25638 appos all,mutants
R7433 T25642 T25614 conj seem,were
R7434 T25643 T25644 det the,histopathologies
R7435 T25644 T25636 dobj histopathologies,showed
R7436 T25645 T25644 amod same,histopathologies
R7437 T25646 T25644 prep of,histopathologies
R7438 T25647 T25648 det the,thymus
R7439 T25648 T25646 pobj thymus,of
R7440 T25649 T25642 punct ", ",seem
R7441 T25650 T25651 det the,thymi
R7442 T25651 T25642 nsubj thymi,seem
R7443 T25652 T25651 amod mutant,thymi
R7444 T25653 T25642 advmod eventually,seem
R7445 T25654 T25655 aux to,result
R7446 T25655 T25642 xcomp result,seem
R7447 T25656 T25655 prep in,result
R7448 T25657 T25658 det the,fate
R7449 T25658 T25656 pobj fate,in
R7450 T25659 T25658 amod same,fate
R7451 T25660 T25642 punct .,seem
R7452 T25662 T25663 nsubj It,is
R7453 T25664 T25663 acomp unclear,is
R7454 T25665 T25666 advmod when,takes
R7455 T25666 T25663 ccomp takes,is
R7456 T25667 T25668 compound K14,cre
R7457 T25668 T25670 compound cre,induction
R7458 T25669 T25668 punct -,cre
R7459 T25670 T25666 nsubj induction,takes
R7460 T25671 T25666 advmod actually,takes
R7461 T25672 T25666 dobj place,takes
R7462 T25673 T25666 prep in,takes
R7463 T25674 T25675 det the,thymus
R7464 T25675 T25673 pobj thymus,in
R7465 T25676 T25675 amod mutant,thymus
R7466 T25677 T25663 punct ", ",is
R7467 T25678 T25663 cc but,is
R7468 T25679 T25680 mark as,were
R7469 T25680 T25700 advcl were,seems
R7470 T25681 T25682 det the,population
R7471 T25682 T25680 nsubj population,were
R7472 T25683 T25682 prep of,population
R7473 T25684 T25683 pobj cells,of
R7474 T25685 T25684 acl showing,cells
R7475 T25686 T25687 det a,staining
R7476 T25687 T25685 dobj staining,showing
R7477 T25688 T25687 amod strong,staining
R7478 T25689 T25687 amod nuclear,staining
R7479 T25690 T25691 compound β,catenin
R7480 T25691 T25687 compound catenin,staining
R7481 T25692 T25691 punct -,catenin
R7482 T25693 T25694 advmod as,as
R7483 T25694 T25682 cc as,population
R7484 T25695 T25694 advmod well,as
R7485 T25696 T25697 det the,cells
R7486 T25697 T25682 conj cells,population
R7487 T25698 T25697 acl expressing,cells
R7488 T25699 T25698 dobj K14,expressing
R7489 T25700 T25663 conj seems,is
R7490 T25701 T25680 acomp small,were
R7491 T25702 T25680 cc and,were
R7492 T25703 T25704 amod thymic,compartments
R7493 T25704 T25706 nsubj compartments,existed
R7494 T25705 T25704 amod epithelial,compartments
R7495 T25706 T25680 conj existed,were
R7496 T25707 T25706 advmod still,existed
R7497 T25708 T25706 prep in,existed
R7498 T25709 T25710 det a,thymus
R7499 T25710 T25708 pobj thymus,in
R7500 T25711 T25710 amod mild,thymus
R7501 T25712 T25710 nmod P3,thymus
R7502 T25713 T25710 amod mutant,thymus
R7503 T25714 T25715 punct (,6E
R7504 T25715 T25706 parataxis 6E,existed
R7505 T25716 T25715 compound Figure,6E
R7506 T25717 T25715 cc and,6E
R7507 T25718 T25715 conj 6F,6E
R7508 T25719 T25715 punct ),6E
R7509 T25720 T25700 punct ", ",seems
R7510 T25721 T25700 nsubj it,seems
R7511 T25722 T25723 mark that,taken
R7512 T25723 T25700 ccomp taken,seems
R7513 T25724 T25725 amod initial,differentiation
R7514 T25725 T25723 nsubj differentiation,taken
R7515 T25726 T25725 prep to,differentiation
R7516 T25727 T25728 amod medullary,TECs
R7517 T25728 T25726 pobj TECs,to
R7518 T25729 T25727 cc and,medullary
R7519 T25730 T25727 conj cortical,medullary
R7520 T25731 T25728 cc and,TECs
R7521 T25732 T25733 compound thymocyte,colonization
R7522 T25733 T25728 conj colonization,TECs
R7523 T25734 T25723 aux have,taken
R7524 T25735 T25723 advmod already,taken
R7525 T25736 T25723 dobj place,taken
R7526 T25737 T25738 amod prior,to
R7527 T25738 T25723 prep to,taken
R7528 T25739 T25740 det the,effects
R7529 T25740 T25738 pobj effects,to
R7530 T25741 T25740 amod major,effects
R7531 T25742 T25740 prep of,effects
R7532 T25743 T25744 npadvmod K14,driven
R7533 T25744 T25746 amod driven,loss
R7534 T25745 T25744 punct -,driven
R7535 T25746 T25742 pobj loss,of
R7536 T25747 T25746 compound Apc,loss
R7537 T25748 T25700 punct .,seems
R7538 T25750 T25751 advmod However,increased
R7539 T25752 T25751 punct ", ",increased
R7540 T25753 T25751 nsubj cells,increased
R7541 T25754 T25753 prep with,cells
R7542 T25755 T25756 amod nuclear,catenin
R7543 T25756 T25759 nmod catenin,cells
R7544 T25757 T25756 nmod β,catenin
R7545 T25758 T25756 punct -,catenin
R7546 T25759 T25754 pobj cells,with
R7547 T25760 T25756 cc and,catenin
R7548 T25761 T25762 npadvmod K8,positive
R7549 T25762 T25756 conj positive,catenin
R7550 T25763 T25761 punct +,K8
R7551 T25764 T25762 npadvmod K14,positive
R7552 T25765 T25764 punct +,K14
R7553 T25766 T25762 amod double,positive
R7554 T25767 T25762 punct -,positive
R7555 T25768 T25759 amod epithelial,cells
R7556 T25769 T25751 advmod subsequently,increased
R7557 T25770 T25751 punct ", ",increased
R7558 T25771 T25751 advcl associated,increased
R7559 T25772 T25771 prep with,associated
R7560 T25773 T25774 amod active,proliferation
R7561 T25774 T25772 pobj proliferation,with
R7562 T25775 T25774 prep in,proliferation
R7563 T25776 T25777 det the,group
R7564 T25777 T25775 pobj group,in
R7565 T25778 T25777 amod latter,group
R7566 T25779 T25777 prep of,group
R7567 T25780 T25779 pobj cells,of
R7568 T25781 T25774 cc and,proliferation
R7569 T25782 T25774 conj loss,proliferation
R7570 T25783 T25782 prep of,loss
R7571 T25784 T25785 compound TEC,compartments
R7572 T25785 T25783 pobj compartments,of
R7573 T25786 T25751 punct .,increased
R7574 T25788 T25789 prep With,became
R7575 T25790 T25788 pobj age,With
R7576 T25791 T25789 punct ", ",became
R7577 T25792 T25793 compound β,catenin
R7578 T25793 T25795 compound catenin,pattern
R7579 T25794 T25793 punct -,catenin
R7580 T25795 T25789 nsubj pattern,became
R7581 T25796 T25795 compound expression,pattern
R7582 T25797 T25798 advmod more,diffuse
R7583 T25798 T25789 acomp diffuse,became
R7584 T25799 T25789 cc and,became
R7585 T25800 T25801 amod fewer,cells
R7586 T25801 T25803 nsubj cells,showed
R7587 T25802 T25801 amod epithelial,cells
R7588 T25803 T25789 conj showed,became
R7589 T25804 T25805 amod nuclear,localization
R7590 T25805 T25803 dobj localization,showed
R7591 T25806 T25803 cc but,showed
R7592 T25807 T25808 nmod K8,cells
R7593 T25808 T25812 nsubj cells,remained
R7594 T25809 T25807 punct +,K8
R7595 T25810 T25808 nmod K14,cells
R7596 T25811 T25810 punct +,K14
R7597 T25812 T25803 conj remained,showed
R7598 T25813 T25812 punct ", ",remained
R7599 T25814 T25812 advcl forming,remained
R7600 T25815 T25816 amod concentric,structures
R7601 T25816 T25814 dobj structures,forming
R7602 T25817 T25816 prep of,structures
R7603 T25818 T25819 amod epithelial,cells
R7604 T25819 T25817 pobj cells,of
R7605 T25820 T25819 acl filled,cells
R7606 T25821 T25820 agent with,filled
R7607 T25822 T25823 amod hard,deposits
R7608 T25823 T25821 pobj deposits,with
R7609 T25824 T25823 compound keratin,deposits
R7610 T25825 T25820 cc and,filled
R7611 T25826 T25820 conj infiltrated,filled
R7612 T25827 T25826 agent with,infiltrated
R7613 T25828 T25829 amod vast,number
R7614 T25829 T25827 pobj number,with
R7615 T25830 T25829 prep of,number
R7616 T25831 T25830 pobj neutrophils,of
R7617 T25832 T25831 cc and,neutrophils
R7618 T25833 T25831 conj macrophages,neutrophils
R7619 T25834 T25789 punct .,became
R7620 T25836 T25837 advmod Only,cells
R7621 T25837 T25841 nsubj cells,dividing
R7622 T25838 T25837 det a,cells
R7623 T25839 T25837 amod few,cells
R7624 T25840 T25837 amod epithelial,cells
R7625 T25842 T25841 aux were,dividing
R7626 T25843 T25841 cc and,dividing
R7627 T25844 T25845 advmod hardly,thymocytes
R7628 T25845 T25847 nsubj thymocytes,were
R7629 T25846 T25845 det any,thymocytes
R7630 T25847 T25841 conj were,dividing
R7631 T25848 T25847 acomp present,were
R7632 T25849 T25847 prep by,were
R7633 T25850 T25851 det this,time
R7634 T25851 T25849 pobj time,by
R7635 T25852 T25847 punct .,were
R7636 T25854 T25855 det These,results
R7637 T25855 T25856 nsubj results,suggest
R7638 T25857 T25858 mark that,took
R7639 T25858 T25856 ccomp took,suggest
R7640 T25859 T25858 prep with,took
R7641 T25860 T25861 det the,deletion
R7642 T25861 T25859 pobj deletion,with
R7643 T25862 T25861 prep of,deletion
R7644 T25863 T25862 pobj Apc,of
R7645 T25864 T25861 prep in,deletion
R7646 T25865 T25864 pobj TECs,in
R7647 T25866 T25858 punct ", ",took
R7648 T25867 T25858 nsubj stabililization,took
R7649 T25868 T25867 cc and,stabililization
R7650 T25869 T25870 amod nuclear,localization
R7651 T25870 T25867 conj localization,stabililization
R7652 T25871 T25867 prep of,stabililization
R7653 T25872 T25873 compound β,catenin
R7654 T25873 T25871 pobj catenin,of
R7655 T25874 T25873 punct -,catenin
R7656 T25875 T25858 dobj place,took
R7657 T25876 T25858 cc and,took
R7658 T25877 T25878 advmod subsequently,differentiated
R7659 T25878 T25858 conj differentiated,took
R7660 T25879 T25880 det these,cells
R7661 T25880 T25878 nsubj cells,differentiated
R7662 T25881 T25878 prep into,differentiated
R7663 T25882 T25881 pobj keratinocytes,into
R7664 T25883 T25884 dep that,expressed
R7665 T25884 T25882 relcl expressed,keratinocytes
R7666 T25885 T25886 preconj both,K14
R7667 T25886 T25884 dobj K14,expressed
R7668 T25887 T25886 cc and,K14
R7669 T25888 T25886 conj K8,K14
R7670 T25889 T25884 punct ", ",expressed
R7671 T25890 T25884 advcl similar,expressed
R7672 T25891 T25890 prep to,similar
R7673 T25892 T25893 det the,cells
R7674 T25893 T25891 pobj cells,to
R7675 T25894 T25893 amod basal,cells
R7676 T25895 T25893 prep of,cells
R7677 T25896 T25897 det the,skin
R7678 T25897 T25895 pobj skin,of
R7679 T25898 T25884 punct ", ",expressed
R7680 T25899 T25900 advmod instead,of
R7681 T25900 T25884 prep of,expressed
R7682 T25901 T25902 compound TEC,subsets
R7683 T25902 T25900 pobj subsets,of
R7684 T25903 T25856 punct .,suggest
R7685 T25905 T25906 det The,expansion
R7686 T25906 T25907 nsubj expansion,lead
R7687 T25908 T25906 cc and,expansion
R7688 T25909 T25906 conj differentiation,expansion
R7689 T25910 T25906 prep of,expansion
R7690 T25911 T25912 det these,keratinocytes
R7691 T25912 T25910 pobj keratinocytes,of
R7692 T25913 T25907 prep to,lead
R7693 T25914 T25913 pobj loss,to
R7694 T25915 T25914 prep of,loss
R7695 T25916 T25917 amod proper,compartments
R7696 T25917 T25915 pobj compartments,of
R7697 T25918 T25917 amod thymic,compartments
R7698 T25919 T25917 amod epithelial,compartments
R7699 T25920 T25907 cc and,lead
R7700 T25921 T25922 prep in,produced
R7701 T25922 T25907 conj produced,lead
R7702 T25923 T25921 pobj turn,in
R7703 T25924 T25922 cc and,produced
R7704 T25925 T25922 conj deposited,produced
R7705 T25926 T25927 det the,keratins
R7706 T25927 T25925 dobj keratins,deposited
R7707 T25928 T25927 amod hard,keratins
R7708 T25929 T25930 dep that,caused
R7709 T25930 T25927 relcl caused,keratins
R7710 T25931 T25930 advmod consequently,caused
R7711 T25932 T25933 amod vast,amount
R7712 T25933 T25934 nsubj amount,infiltrate
R7713 T25934 T25930 ccomp infiltrate,caused
R7714 T25935 T25933 prep of,amount
R7715 T25936 T25935 pobj neutrophils,of
R7716 T25937 T25936 cc and,neutrophils
R7717 T25938 T25936 conj macrophages,neutrophils
R7718 T25939 T25934 aux to,infiltrate
R7719 T25940 T25941 det the,thymus
R7720 T25941 T25934 dobj thymus,infiltrate
R7721 T25942 T25907 punct .,lead
R7722 T25944 T25945 det These,structures
R7723 T25945 T25948 nsubj structures,overtaken
R7724 T25946 T25945 amod aberrant,structures
R7725 T25947 T25945 amod epithelial,structures
R7726 T25949 T25948 advmod eventually,overtaken
R7727 T25950 T25948 aux have,overtaken
R7728 T25951 T25952 det the,whole
R7729 T25952 T25948 dobj whole,overtaken
R7730 T25953 T25952 prep of,whole
R7731 T25954 T25955 det the,thymus
R7732 T25955 T25953 pobj thymus,of
R7733 T25956 T25948 cc and,overtaken
R7734 T25957 T25948 conj driven,overtaken
R7735 T25958 T25957 prt out,driven
R7736 T25959 T25960 det the,thymocytes
R7737 T25960 T25957 dobj thymocytes,driven
R7738 T25961 T25960 amod colonized,thymocytes
R7739 T25962 T25948 punct .,overtaken
R7740 T25964 T25965 npadvmod K14,driven
R7741 T25965 T25967 amod driven,loss
R7742 T25966 T25965 punct -,driven
R7743 T25967 T25968 nsubj loss,misdirected
R7744 T25969 T25967 prep of,loss
R7745 T25970 T25969 pobj Apc,of
R7746 T25971 T25967 cc and,loss
R7747 T25972 T25973 amod subsequent,expression
R7748 T25973 T25967 conj expression,loss
R7749 T25974 T25973 amod constitutive,expression
R7750 T25975 T25973 prep of,expression
R7751 T25976 T25977 compound β,catenin
R7752 T25977 T25975 pobj catenin,of
R7753 T25978 T25977 punct -,catenin
R7754 T25979 T25973 prep in,expression
R7755 T25980 T25979 pobj TECs,in
R7756 T25981 T25968 aux have,misdirected
R7757 T25982 T25968 advmod therefore,misdirected
R7758 T25983 T25968 dobj them,misdirected
R7759 T25984 T25968 prep to,misdirected
R7760 T25985 T25986 amod wrong,fate
R7761 T25986 T25984 pobj fate,to
R7762 T25987 T25986 amod epithelial,fate
R7763 T25988 T25986 compound cell,fate
R7764 T25989 T25968 punct ", ",misdirected
R7765 T25990 T25991 neg not,allowing
R7766 T25991 T25968 advcl allowing,misdirected
R7767 T25992 T25993 amod proper,differentiation
R7768 T25993 T25991 dobj differentiation,allowing
R7769 T25994 T25993 prep to,differentiation
R7770 T25995 T25996 preconj either,cortical
R7771 T25996 T25997 amod cortical,TECs
R7772 T25997 T25994 pobj TECs,to
R7773 T25998 T25996 cc or,cortical
R7774 T25999 T25996 conj medullary,cortical
R7775 T26000 T25993 punct ", ",differentiation
R7776 T26001 T26002 dep which,is
R7777 T26002 T25993 relcl is,differentiation
R7778 T26003 T26002 acomp essential,is
R7779 T26004 T26003 prep for,essential
R7780 T26005 T26006 amod normal,development
R7781 T26006 T26004 pobj development,for
R7782 T26007 T26006 compound thymocyte,development
R7783 T26008 T25968 punct .,misdirected
R7784 T26010 T26011 nsubj This,is
R7785 T26012 T26011 preconj not,is
R7786 T26013 T26012 advmod only,not
R7787 T26014 T26011 conj evident,is
R7788 T26015 T26014 prep from,evident
R7789 T26016 T26017 det the,lack
R7790 T26017 T26015 pobj lack,from
R7791 T26018 T26017 prep of,lack
R7792 T26019 T26020 amod dividing,thymocytes
R7793 T26020 T26018 pobj thymocytes,of
R7794 T26021 T26017 prep in,lack
R7795 T26022 T26023 det the,thymus
R7796 T26023 T26021 pobj thymus,in
R7797 T26024 T26023 amod mutant,thymus
R7798 T26025 T26017 prep by,lack
R7799 T26026 T26025 pobj P13,by
R7800 T26027 T26015 punct ", ",from
R7801 T26028 T26015 cc but,from
R7802 T26029 T26028 advmod also,but
R7803 T26030 T26015 conj by,from
R7804 T26031 T26032 det the,pattern
R7805 T26032 T26030 pobj pattern,by
R7806 T26033 T26032 amod differential,pattern
R7807 T26034 T26032 compound expression,pattern
R7808 T26035 T26032 prep of,pattern
R7809 T26036 T26035 pobj keratins,of
R7810 T26037 T26036 punct ", ",keratins
R7811 T26038 T26039 dep which,were
R7812 T26039 T26036 relcl were,keratins
R7813 T26040 T26041 advmod more,like
R7814 T26041 T26039 acomp like,were
R7815 T26042 T26041 npadvmod skin,like
R7816 T26043 T26041 punct -,like
R7817 T26044 T26041 prep than,like
R7818 T26045 T26046 npadvmod TEC,like
R7819 T26046 T26044 amod like,than
R7820 T26047 T26046 punct -,like
R7821 T26048 T26011 punct .,is
R7822 T26050 T26051 det The,importance
R7823 T26051 T26052 nsubjpass importance,demonstrated
R7824 T26053 T26051 prep of,importance
R7825 T26054 T26055 compound Apc,function
R7826 T26055 T26053 pobj function,of
R7827 T26056 T26051 prep in,importance
R7828 T26057 T26058 amod thymic,development
R7829 T26058 T26056 pobj development,in
R7830 T26059 T26052 aux has,demonstrated
R7831 T26060 T26052 auxpass been,demonstrated
R7832 T26061 T26052 agent by,demonstrated
R7833 T26062 T26063 npadvmod thymocyte,specific
R7834 T26063 T26065 amod specific,loss
R7835 T26064 T26063 punct -,specific
R7836 T26065 T26061 pobj loss,by
R7837 T26066 T26065 prep of,loss
R7838 T26067 T26066 pobj Apc,of
R7839 T26068 T26065 prep by,loss
R7840 T26069 T26068 pcomp crossing,by
R7841 T26070 T26071 det a,strain
R7842 T26071 T26069 dobj strain,crossing
R7843 T26072 T26071 amod different,strain
R7844 T26073 T26071 prep of,strain
R7845 T26074 T26075 nmod Apc,mice
R7846 T26075 T26073 pobj mice,of
R7847 T26076 T26075 amod conditional,mice
R7848 T26077 T26075 cc and,mice
R7849 T26078 T26079 nmod LckCre,mice
R7850 T26079 T26075 conj mice,mice
R7851 T26080 T26079 amod transgenic,mice
R7852 T26081 T26082 punct [,33
R7853 T26082 T26052 parataxis 33,demonstrated
R7854 T26083 T26082 punct ],33
R7855 T26084 T26052 punct .,demonstrated
R7856 T26086 T26087 advmod Here,demonstrated
R7857 T26088 T26087 punct ", ",demonstrated
R7858 T26089 T26087 prep by,demonstrated
R7859 T26090 T26091 npadvmod K14,driven
R7860 T26091 T26093 amod driven,loss
R7861 T26092 T26091 punct -,driven
R7862 T26093 T26089 pobj loss,by
R7863 T26094 T26095 npadvmod TEC,specific
R7864 T26095 T26093 amod specific,loss
R7865 T26096 T26095 punct -,specific
R7866 T26097 T26093 prep of,loss
R7867 T26098 T26097 pobj Apc,of
R7868 T26099 T26087 punct ", ",demonstrated
R7869 T26100 T26087 nsubj we,demonstrated
R7870 T26101 T26087 aux have,demonstrated
R7871 T26102 T26103 poss its,importance
R7872 T26103 T26087 dobj importance,demonstrated
R7873 T26104 T26103 prep in,importance
R7874 T26105 T26106 compound thymus,development
R7875 T26106 T26104 pobj development,in
R7876 T26107 T26108 preconj not,in
R7877 T26108 T26087 prep in,demonstrated
R7878 T26109 T26107 advmod only,not
R7879 T26110 T26108 pobj thymocytes,in
R7880 T26111 T26108 cc but,in
R7881 T26112 T26111 advmod also,but
R7882 T26113 T26108 conj in,in
R7883 T26114 T26113 pobj TECs,in
R7884 T26115 T26087 punct .,demonstrated
R7885 T26117 T26118 nsubj It,is
R7886 T26119 T26118 prep of,is
R7887 T26120 T26119 pobj interest,of
R7888 T26121 T26122 mark that,seen
R7889 T26122 T26118 ccomp seen,is
R7890 T26123 T26124 amod dental,abnormalities
R7891 T26124 T26122 nsubjpass abnormalities,seen
R7892 T26125 T26124 punct ", ",abnormalities
R7893 T26126 T26127 amod such,as
R7894 T26127 T26124 prep as,abnormalities
R7895 T26128 T26129 amod supernumerary,teeth
R7896 T26129 T26127 pobj teeth,as
R7897 T26130 T26128 cc and,supernumerary
R7898 T26131 T26128 conj impacted,supernumerary
R7899 T26132 T26129 amod similar,teeth
R7900 T26133 T26132 prep to,similar
R7901 T26134 T26133 pobj those,to
R7902 T26135 T26134 acl observed,those
R7903 T26136 T26135 prep in,observed
R7904 T26137 T26138 poss our,mice
R7905 T26138 T26136 pobj mice,in
R7906 T26139 T26138 amod mutant,mice
R7907 T26140 T26122 punct ", ",seen
R7908 T26141 T26122 auxpass are,seen
R7909 T26142 T26122 advmod frequently,seen
R7910 T26143 T26122 prep in,seen
R7911 T26144 T26143 pobj patients,in
R7912 T26145 T26144 prep with,patients
R7913 T26146 T26147 poss Gardner,syndrome
R7914 T26147 T26145 pobj syndrome,with
R7915 T26148 T26146 case 's,Gardner
R7916 T26149 T26144 punct ", ",patients
R7917 T26150 T26144 appos carriers,patients
R7918 T26151 T26150 prep of,carriers
R7919 T26152 T26153 compound APC,mutation
R7920 T26153 T26151 pobj mutation,of
R7921 T26154 T26153 compound germline,mutation
R7922 T26155 T26156 punct [,6
R7923 T26156 T26122 parataxis 6,seen
R7924 T26157 T26156 punct ],6
R7925 T26158 T26118 punct .,is
R7926 T26160 T26161 det The,importance
R7927 T26161 T26162 nsubjpass importance,pointed
R7928 T26163 T26161 prep of,importance
R7929 T26164 T26165 npadvmod odonto,stomatological
R7930 T26165 T26167 amod stomatological,examinations
R7931 T26166 T26165 punct -,stomatological
R7932 T26167 T26163 pobj examinations,of
R7933 T26168 T26162 aux should,pointed
R7934 T26169 T26162 advmod hence,pointed
R7935 T26170 T26162 auxpass be,pointed
R7936 T26171 T26162 prt out,pointed
R7937 T26172 T26162 prep as,pointed
R7938 T26173 T26174 det a,means
R7939 T26174 T26172 pobj means,as
R7940 T26175 T26174 prep of,means
R7941 T26176 T26175 pcomp reaching,of
R7942 T26177 T26178 det a,diagnosis
R7943 T26178 T26176 dobj diagnosis,reaching
R7944 T26179 T26178 amod presumptive,diagnosis
R7945 T26180 T26178 punct ", ",diagnosis
R7946 T26181 T26182 poss whose,confirmation
R7947 T26182 T26183 dep confirmation,is
R7948 T26183 T26178 relcl is,diagnosis
R7949 T26184 T26183 acomp vital,is
R7950 T26185 T26184 prep to,vital
R7951 T26186 T26187 det the,patient
R7952 T26187 T26185 pobj patient,to
R7953 T26188 T26162 punct .,pointed
R7954 T26190 T26191 amod Further,characterization
R7955 T26191 T26192 nsubj characterization,provide
R7956 T26193 T26191 prep of,characterization
R7957 T26194 T26195 det the,mechanism
R7958 T26195 T26193 pobj mechanism,of
R7959 T26196 T26195 prep of,mechanism
R7960 T26197 T26198 amod such,defects
R7961 T26198 T26196 pobj defects,of
R7962 T26199 T26198 amod developmental,defects
R7963 T26200 T26191 acl using,characterization
R7964 T26201 T26202 poss our,model
R7965 T26202 T26200 dobj model,using
R7966 T26203 T26202 compound mouse,model
R7967 T26204 T26192 aux should,provide
R7968 T26205 T26206 amod important,insights
R7969 T26206 T26192 dobj insights,provide
R7970 T26207 T26192 prep into,provide
R7971 T26208 T26209 compound Apc,function
R7972 T26209 T26207 pobj function,into
R7973 T26210 T26209 prep in,function
R7974 T26211 T26212 amod multiple,systems
R7975 T26212 T26210 pobj systems,in
R7976 T26213 T26212 compound organ,systems
R7977 T26214 T26192 cc and,provide
R7978 T26215 T26216 dep to,give
R7979 T26216 T26192 conj give,provide
R7980 T26217 T26218 amod better,insights
R7981 T26218 T26216 dobj insights,give
R7982 T26219 T26218 prep into,insights
R7983 T26220 T26221 amod potential,events
R7984 T26221 T26219 pobj events,into
R7985 T26222 T26221 amod adverse,events
R7986 T26223 T26221 prep in,events
R7987 T26224 T26225 amod human,subjects
R7988 T26225 T26223 pobj subjects,in
R7989 T26226 T26192 punct .,provide
R7990 T26228 T26229 prep In,shown
R7991 T26230 T26228 pobj conclusion,In
R7992 T26231 T26229 punct ", ",shown
R7993 T26232 T26229 nsubj we,shown
R7994 T26233 T26229 aux have,shown
R7995 T26234 T26235 mark that,causes
R7996 T26235 T26229 ccomp causes,shown
R7997 T26236 T26235 nsubj loss,causes
R7998 T26237 T26236 prep of,loss
R7999 T26238 T26237 pobj Apc,of
R8000 T26239 T26236 prep in,loss
R8001 T26240 T26241 npadvmod K14,expressing
R8002 T26241 T26243 amod expressing,cells
R8003 T26242 T26241 punct -,expressing
R8004 T26243 T26239 pobj cells,in
R8005 T26244 T26243 amod embryonic,cells
R8006 T26245 T26246 amod aberrant,morphogenesis
R8007 T26246 T26235 dobj morphogenesis,causes
R8008 T26247 T26235 prep in,causes
R8009 T26248 T26249 amod various,appendages
R8010 T26249 T26247 pobj appendages,in
R8011 T26250 T26249 compound skin,appendages
R8012 T26251 T26249 punct ", ",appendages
R8013 T26252 T26249 prep including,appendages
R8014 T26253 T26254 compound hair,follicles
R8015 T26254 T26252 pobj follicles,including
R8016 T26255 T26254 cc and,follicles
R8017 T26256 T26254 conj teeth,follicles
R8018 T26257 T26256 punct ", ",teeth
R8019 T26258 T26256 cc and,teeth
R8020 T26259 T26260 amod abnormal,organogensis
R8021 T26260 T26256 conj organogensis,teeth
R8022 T26261 T26260 compound thymus,organogensis
R8023 T26262 T26229 punct .,shown
R8024 T26264 T26265 poss Our,results
R8025 T26265 T26266 nsubj results,provide
R8026 T26267 T26268 amod genetic,evidence
R8027 T26268 T26266 dobj evidence,provide
R8028 T26269 T26270 mark that,is
R8029 T26270 T26268 acl is,evidence
R8030 T26271 T26270 nsubj expression,is
R8031 T26272 T26271 prep of,expression
R8032 T26273 T26272 pobj Apc,of
R8033 T26274 T26270 acomp essential,is
R8034 T26275 T26274 prep for,essential
R8035 T26276 T26275 pobj regulation,for
R8036 T26277 T26276 prep of,regulation
R8037 T26278 T26279 amod proper,fates
R8038 T26279 T26277 pobj fates,of
R8039 T26280 T26279 compound cell,fates
R8040 T26281 T26276 prep in,regulation
R8041 T26282 T26283 det these,organs
R8042 T26283 T26281 pobj organs,in
R8043 T26284 T26285 dep that,require
R8044 T26285 T26283 relcl require,organs
R8045 T26286 T26287 amod epithelial,mesenchymal
R8046 T26287 T26289 amod mesenchymal,interactions
R8047 T26288 T26287 punct –,mesenchymal
R8048 T26289 T26285 dobj interactions,require
R8049 T26290 T26266 punct .,provide
R8050 T26538 T26537 prep of,Construction
R8051 T26539 T26540 compound targeting,vectors
R8052 T26540 T26538 pobj vectors,of
R8053 T26541 T26537 punct .,Construction
R8054 T26543 T26544 aux To,target
R8055 T26544 T26545 advcl target,obtained
R8056 T26546 T26547 det the,locus
R8057 T26547 T26544 dobj locus,target
R8058 T26548 T26547 compound Apc,locus
R8059 T26549 T26545 punct ", ",obtained
R8060 T26550 T26545 nsubj we,obtained
R8061 T26551 T26552 compound BAC,clone
R8062 T26552 T26545 dobj clone,obtained
R8063 T26553 T26554 compound RP23,233F17
R8064 T26554 T26552 appos 233F17,clone
R8065 T26555 T26554 punct -,233F17
R8066 T26556 T26557 dep that,contains
R8067 T26557 T26552 relcl contains,clone
R8068 T26558 T26559 predet all,sequence
R8069 T26559 T26557 dobj sequence,contains
R8070 T26560 T26559 det the,sequence
R8071 T26561 T26559 prep of,sequence
R8072 T26562 T26561 pobj Apc,of
R8073 T26563 T26559 prep except,sequence
R8074 T26564 T26563 prep for,except
R8075 T26565 T26566 det the,UTR
R8076 T26566 T26564 pobj UTR,for
R8077 T26567 T26566 nummod 5,UTR
R8078 T26568 T26567 punct ′,5
R8079 T26569 T26566 cc and,UTR
R8080 T26570 T26566 conj exon,UTR
R8081 T26571 T26570 nummod 1,exon
R8082 T26572 T26545 punct .,obtained
R8083 T26574 T26575 advcl Using,conducted
R8084 T26576 T26577 det a,method
R8085 T26577 T26574 dobj method,Using
R8086 T26578 T26579 npadvmod recombineering,based
R8087 T26579 T26577 amod based,method
R8088 T26580 T26579 punct -,based
R8089 T26581 T26577 prep for,method
R8090 T26582 T26581 pcomp generating,for
R8091 T26583 T26584 amod conditional,mutations
R8092 T26584 T26582 dobj mutations,generating
R8093 T26585 T26586 punct [,13
R8094 T26586 T26574 parataxis 13,Using
R8095 T26587 T26586 nummod 12,13
R8096 T26588 T26586 punct ",",13
R8097 T26589 T26586 punct ],13
R8098 T26590 T26575 punct ", ",conducted
R8099 T26591 T26575 nsubjpass subcloning,conducted
R8100 T26592 T26591 prep of,subcloning
R8101 T26593 T26592 pobj BAC,of
R8102 T26594 T26591 cc and,subcloning
R8103 T26595 T26596 amod further,modifications
R8104 T26596 T26591 conj modifications,subcloning
R8105 T26597 T26575 auxpass were,conducted
R8106 T26598 T26575 punct .,conducted
R8107 T26600 T26601 det The,sequence
R8108 T26601 T26603 nsubjpass sequence,subcloned
R8109 T26602 T26601 amod genomic,sequence
R8110 T26604 T26601 acl encompassing,sequence
R8111 T26605 T26606 nmod Apc,11
R8112 T26606 T26604 dobj 11,encompassing
R8113 T26607 T26606 nmod exons,11
R8114 T26608 T26606 prep to,11
R8115 T26609 T26608 pobj 15,to
R8116 T26610 T26603 auxpass was,subcloned
R8117 T26611 T26603 advmod first,subcloned
R8118 T26612 T26603 prep into,subcloned
R8119 T26613 T26614 compound pBR322,vector
R8120 T26614 T26612 pobj vector,into
R8121 T26615 T26603 punct ", ",subcloned
R8122 T26616 T26603 cc and,subcloned
R8123 T26617 T26618 advmod then,followed
R8124 T26618 T26603 conj followed,subcloned
R8125 T26619 T26620 det a,site
R8126 T26620 T26618 nsubjpass site,followed
R8127 T26621 T26620 compound loxP,site
R8128 T26622 T26618 auxpass was,followed
R8129 T26623 T26618 aux introduced,followed
R8130 T26624 T26618 prep into,followed
R8131 T26625 T26624 pobj intron,into
R8132 T26626 T26625 nummod 13,intron
R8133 T26627 T26618 agent by,followed
R8134 T26628 T26629 nmod loxP,FRT
R8135 T26629 T26631 nmod FRT,cassette
R8136 T26630 T26629 punct -,FRT
R8137 T26631 T26627 pobj cassette,by
R8138 T26632 T26629 punct -,FRT
R8139 T26633 T26634 compound PGKneor,FRT
R8140 T26634 T26629 appos FRT,FRT
R8141 T26635 T26634 punct -,FRT
R8142 T26636 T26631 compound selection,cassette
R8143 T26637 T26631 prep into,cassette
R8144 T26638 T26637 pobj intron14,into
R8145 T26639 T26638 prep of,intron14
R8146 T26640 T26641 det the,gene
R8147 T26641 T26639 pobj gene,of
R8148 T26642 T26641 compound Apc,gene
R8149 T26643 T26644 punct (,1A
R8150 T26644 T26618 parataxis 1A,followed
R8151 T26645 T26644 compound Figure,1A
R8152 T26646 T26644 punct ),1A
R8153 T26647 T26618 punct .,followed
R8156 T27081 T27080 prep of,Generation
R8157 T27082 T27083 compound ApcCKO,cells
R8158 T27083 T27081 pobj cells,of
R8159 T27084 T27083 compound ES,cells
R8160 T27085 T27083 cc and,cells
R8161 T27086 T27083 conj mice,cells
R8162 T27087 T27080 punct .,Generation
R8163 T27089 T27090 det The,vectors
R8164 T27090 T27093 nsubjpass vectors,electroporated
R8165 T27091 T27090 amod linearized,vectors
R8166 T27092 T27090 compound targeting,vectors
R8167 T27094 T27093 auxpass were,electroporated
R8168 T27095 T27093 prep into,electroporated
R8169 T27096 T27097 nummod 129,S
R8170 T27097 T27099 npadvmod S,derived
R8171 T27098 T27097 punct /,S
R8172 T27099 T27101 amod derived,cells
R8173 T27100 T27099 punct -,derived
R8174 T27101 T27095 pobj cells,into
R8175 T27102 T27101 compound ES,cells
R8176 T27103 T27101 punct ", ",cells
R8177 T27104 T27105 compound WW6,cells
R8178 T27105 T27101 appos cells,cells
R8179 T27106 T27107 punct [,15
R8180 T27107 T27093 parataxis 15,electroporated
R8181 T27108 T27107 punct ],15
R8182 T27109 T27093 punct .,electroporated
R8183 T27111 T27112 det All,clones
R8184 T27112 T27118 nsubjpass clones,screened
R8185 T27113 T27112 nmod candidate,clones
R8186 T27114 T27115 npadvmod G418,resistant
R8187 T27115 T27112 amod resistant,clones
R8188 T27116 T27115 punct -,resistant
R8189 T27117 T27112 compound ES,clones
R8190 T27119 T27118 auxpass were,screened
R8191 T27120 T27118 prep by,screened
R8192 T27121 T27122 amod long,range
R8193 T27122 T27124 nmod range,PCR
R8194 T27123 T27122 punct -,range
R8195 T27124 T27120 pobj PCR,by
R8196 T27125 T27126 npadvmod gene,specific
R8197 T27126 T27124 amod specific,PCR
R8198 T27127 T27126 punct -,specific
R8199 T27128 T27124 acl using,PCR
R8200 T27129 T27130 compound Expand,System
R8201 T27130 T27128 dobj System,using
R8202 T27131 T27132 compound Long,Template
R8203 T27132 T27130 compound Template,System
R8204 T27133 T27130 compound PCR,System
R8205 T27134 T27135 punct (,Roche
R8206 T27135 T27130 parataxis Roche,System
R8207 T27136 T27135 punct ", ",Roche
R8208 T27137 T27135 npadvmod Indianapolis,Roche
R8209 T27138 T27135 punct ", ",Roche
R8210 T27139 T27135 npadvmod Indiana,Roche
R8211 T27140 T27135 punct ", ",Roche
R8212 T27141 T27142 compound United,States
R8213 T27142 T27135 npadvmod States,Roche
R8214 T27143 T27135 punct ),Roche
R8215 T27144 T27124 punct ", ",PCR
R8216 T27145 T27124 acl followed,PCR
R8217 T27146 T27145 agent by,followed
R8218 T27147 T27146 pobj sequencing,by
R8219 T27148 T27149 aux to,validate
R8220 T27149 T27147 advcl validate,sequencing
R8221 T27150 T27151 det the,insertion
R8222 T27151 T27149 dobj insertion,validate
R8223 T27152 T27151 amod correct,insertion
R8224 T27153 T27151 prep of,insertion
R8225 T27154 T27155 det the,site
R8226 T27155 T27153 pobj site,of
R8227 T27156 T27157 amod single,loxP
R8228 T27157 T27155 compound loxP,site
R8229 T27158 T27155 cc and,site
R8230 T27159 T27160 det the,cassette
R8231 T27160 T27155 conj cassette,site
R8232 T27161 T27160 compound selection,cassette
R8233 T27162 T27118 punct .,screened
R8234 T27164 T27165 nummod Two,clones
R8235 T27165 T27167 nsubjpass clones,injected
R8236 T27166 T27165 compound ES,clones
R8237 T27168 T27165 prep with,clones
R8238 T27169 T27170 amod correct,modification
R8239 T27170 T27168 pobj modification,with
R8240 T27171 T27170 nmod ApcCKON,modification
R8241 T27172 T27171 punct /,ApcCKON
R8242 T27173 T27171 punct +,ApcCKON
R8243 T27174 T27167 auxpass were,injected
R8244 T27175 T27167 prep into,injected
R8245 T27176 T27177 compound C57BL,6J
R8246 T27177 T27179 compound 6J,blastocysts
R8247 T27178 T27177 punct /,6J
R8248 T27179 T27175 pobj blastocysts,into
R8249 T27180 T27167 punct ", ",injected
R8250 T27181 T27182 prep after,backcrossed
R8251 T27182 T27167 advcl backcrossed,injected
R8252 T27183 T27181 pobj which,after
R8253 T27184 T27185 amod chimeric,mice
R8254 T27185 T27182 nsubjpass mice,backcrossed
R8255 T27186 T27185 prep with,mice
R8256 T27187 T27188 amod high,levels
R8257 T27188 T27186 pobj levels,with
R8258 T27189 T27188 prep of,levels
R8259 T27190 T27191 compound ES,cell
R8260 T27191 T27192 compound cell,contribution
R8261 T27192 T27189 pobj contribution,of
R8262 T27193 T27182 auxpass were,backcrossed
R8263 T27194 T27182 prep to,backcrossed
R8264 T27195 T27196 compound C57BL,6J
R8265 T27196 T27198 compound 6J,females
R8266 T27197 T27196 punct /,6J
R8267 T27198 T27194 pobj females,to
R8268 T27199 T27200 aux to,produce
R8269 T27200 T27182 advcl produce,backcrossed
R8270 T27201 T27202 amod heterozygous,offspring
R8271 T27202 T27200 dobj offspring,produce
R8272 T27203 T27202 compound F1,offspring
R8273 T27204 T27167 punct .,injected
R8274 T27206 T27207 det The,samples
R8275 T27207 T27210 nsubjpass samples,analyzed
R8276 T27208 T27207 amod genomic,samples
R8277 T27209 T27207 compound DNA,samples
R8278 T27211 T27207 acl obtained,samples
R8279 T27212 T27211 prep from,obtained
R8280 T27213 T27214 det the,tail
R8281 T27214 T27212 pobj tail,from
R8282 T27215 T27214 prep of,tail
R8283 T27216 T27217 compound F1,offspring
R8284 T27217 T27215 pobj offspring,of
R8285 T27218 T27210 auxpass were,analyzed
R8286 T27219 T27210 advmod subsequently,analyzed
R8287 T27220 T27210 prep by,analyzed
R8288 T27221 T27222 compound Southern,blot
R8289 T27222 T27223 compound blot,analysis
R8290 T27223 T27220 pobj analysis,by
R8291 T27224 T27225 aux to,confirm
R8292 T27225 T27210 advcl confirm,analyzed
R8293 T27226 T27225 advmod further,confirm
R8294 T27227 T27228 det the,recombination
R8295 T27228 T27225 dobj recombination,confirm
R8296 T27229 T27228 amod correct,recombination
R8297 T27230 T27228 amod homologous,recombination
R8298 T27231 T27210 punct .,analyzed
R8299 T27233 T27234 prep By,deleted
R8300 T27235 T27233 pcomp crossing,By
R8301 T27236 T27237 det the,mice
R8302 T27237 T27235 dobj mice,crossing
R8303 T27238 T27237 amod heterozygous,mice
R8304 T27239 T27235 prep to,crossing
R8305 T27240 T27241 compound FLPe,mice
R8306 T27241 T27239 pobj mice,to
R8307 T27242 T27241 compound deleter,mice
R8308 T27243 T27244 punct [,34
R8309 T27244 T27235 parataxis 34,crossing
R8310 T27245 T27244 punct ],34
R8311 T27246 T27234 punct ", ",deleted
R8312 T27247 T27248 compound PGKneor,cassette
R8313 T27248 T27234 nsubjpass cassette,deleted
R8314 T27249 T27234 auxpass was,deleted
R8315 T27250 T27234 prep in,deleted
R8316 T27251 T27252 det the,germline
R8317 T27252 T27250 pobj germline,in
R8318 T27253 T27234 prep by,deleted
R8319 T27254 T27255 npadvmod FRT,mediated
R8320 T27255 T27257 amod mediated,recombination
R8321 T27256 T27255 punct -,mediated
R8322 T27257 T27253 pobj recombination,by
R8323 T27258 T27259 aux to,generate
R8324 T27259 T27234 advcl generate,deleted
R8325 T27260 T27259 dobj mice,generate
R8326 T27261 T27260 prep with,mice
R8327 T27262 T27263 det the,allele
R8328 T27263 T27261 pobj allele,with
R8329 T27264 T27263 amod final,allele
R8330 T27265 T27263 compound ApcCKO,allele
R8331 T27266 T27234 punct .,deleted
R8332 T27268 T27269 nmod ApcCKO,mice
R8333 T27269 T27271 nsubjpass mice,crossed
R8334 T27270 T27269 amod heterozygous,mice
R8335 T27272 T27271 auxpass were,crossed
R8336 T27273 T27271 advmod together,crossed
R8337 T27274 T27275 aux to,generate
R8338 T27275 T27271 advcl generate,crossed
R8339 T27276 T27277 amod homozygous,mice
R8340 T27277 T27275 dobj mice,generate
R8341 T27278 T27271 punct ", ",crossed
R8342 T27279 T27271 cc and,crossed
R8343 T27280 T27281 det the,offspring
R8344 T27281 T27283 nsubjpass offspring,interbred
R8345 T27282 T27281 amod homozygous,offspring
R8346 T27283 T27271 conj interbred,crossed
R8347 T27284 T27283 auxpass were,interbred
R8348 T27285 T27283 prep for,interbred
R8349 T27286 T27285 pobj maintenance,for
R8350 T27287 T27283 punct .,interbred
R8351 T27432 T27431 prep of,Generation
R8352 T27433 T27434 compound ApcΔ580,mice
R8353 T27434 T27432 pobj mice,of
R8354 T27435 T27431 punct .,Generation
R8355 T27437 T27438 compound ApcCKO,mice
R8356 T27438 T27440 nsubjpass mice,crossed
R8357 T27439 T27438 compound heterozygote,mice
R8358 T27441 T27440 auxpass were,crossed
R8359 T27442 T27440 prep with,crossed
R8360 T27443 T27444 compound Cre,mice
R8361 T27444 T27442 pobj mice,with
R8362 T27445 T27444 compound deleter,mice
R8363 T27446 T27444 punct ", ",mice
R8364 T27447 T27448 compound EIIA,cre
R8365 T27448 T27450 npadvmod cre,transgenic
R8366 T27449 T27448 punct -,cre
R8367 T27450 T27451 amod transgenic,mice
R8368 T27451 T27444 appos mice,mice
R8369 T27452 T27453 dep that,express
R8370 T27453 T27451 relcl express,mice
R8371 T27454 T27453 dobj Cre,express
R8372 T27455 T27453 prep in,express
R8373 T27456 T27457 amod early,embryo
R8374 T27457 T27455 pobj embryo,in
R8375 T27458 T27459 punct [,35
R8376 T27459 T27444 parataxis 35,mice
R8377 T27460 T27459 punct ],35
R8378 T27461 T27440 punct ", ",crossed
R8379 T27462 T27463 aux to,knockout
R8380 T27463 T27440 advcl knockout,crossed
R8381 T27464 T27465 det the,allele
R8382 T27465 T27463 dobj allele,knockout
R8383 T27466 T27465 compound Apc,allele
R8384 T27467 T27463 prep in,knockout
R8385 T27468 T27469 det the,germline
R8386 T27469 T27467 pobj germline,in
R8387 T27470 T27463 punct ", ",knockout
R8388 T27471 T27472 advmod consequently,creating
R8389 T27472 T27463 advcl creating,knockout
R8390 T27473 T27474 det a,strain
R8391 T27474 T27472 dobj strain,creating
R8392 T27475 T27474 compound knockout,strain
R8393 T27476 T27477 punct (,1A
R8394 T27477 T27440 parataxis 1A,crossed
R8395 T27478 T27477 compound Figure,1A
R8396 T27479 T27477 punct ),1A
R8397 T27480 T27440 punct .,crossed
R8398 T27482 T27483 det The,mice
R8399 T27483 T27488 nsubjpass mice,maintained
R8400 T27484 T27483 amod resultant,mice
R8401 T27485 T27483 nmod ApcΔ580,mice
R8402 T27486 T27485 punct /,ApcΔ580
R8403 T27487 T27485 punct +,ApcΔ580
R8404 T27489 T27488 auxpass were,maintained
R8405 T27490 T27488 prep by,maintained
R8406 T27491 T27490 pcomp backcrossing,by
R8407 T27492 T27491 prep to,backcrossing
R8408 T27493 T27494 compound C57BL,6J
R8409 T27494 T27496 compound 6J,females
R8410 T27495 T27494 punct /,6J
R8411 T27496 T27492 pobj females,to
R8412 T27497 T27488 punct .,maintained
R8413 T27691 T27690 prep of,Generation
R8414 T27692 T27693 nmod K14,cre
R8415 T27693 T27695 nmod cre,mice
R8416 T27694 T27693 punct -,cre
R8417 T27695 T27691 pobj mice,of
R8418 T27696 T27693 punct ;,cre
R8419 T27697 T27698 compound ApcCKO,CKO
R8420 T27698 T27693 appos CKO,cre
R8421 T27699 T27698 punct /,CKO
R8422 T27700 T27690 punct .,Generation
R8423 T27702 T27703 det The,mice
R8424 T27703 T27704 nsubjpass mice,generated
R8425 T27705 T27703 acl analyzed,mice
R8426 T27706 T27705 prep in,analyzed
R8427 T27707 T27708 det this,study
R8428 T27708 T27706 pobj study,in
R8429 T27709 T27704 auxpass were,generated
R8430 T27710 T27704 prep by,generated
R8431 T27711 T27710 pcomp crossing,by
R8432 T27712 T27713 compound ApcCKO,mice
R8433 T27713 T27711 dobj mice,crossing
R8434 T27714 T27713 compound heterozygote,mice
R8435 T27715 T27713 prep of,mice
R8436 T27716 T27717 det the,generation
R8437 T27717 T27715 pobj generation,of
R8438 T27718 T27717 compound F1,generation
R8439 T27719 T27720 punct (,background
R8440 T27720 T27717 parataxis background,generation
R8441 T27721 T27722 nmod C57BL,6J
R8442 T27722 T27720 nmod 6J,background
R8443 T27723 T27722 punct /,6J
R8444 T27724 T27722 punct ×,6J
R8445 T27725 T27726 nummod 129,S
R8446 T27726 T27722 appos S,6J
R8447 T27727 T27726 punct /,S
R8448 T27728 T27720 punct ),background
R8449 T27729 T27711 prep with,crossing
R8450 T27730 T27731 compound K14,cre
R8451 T27731 T27733 npadvmod cre,transgenic
R8452 T27732 T27731 punct -,cre
R8453 T27733 T27734 amod transgenic,mice
R8454 T27734 T27729 pobj mice,with
R8455 T27735 T27736 punct (,background
R8456 T27736 T27734 parataxis background,mice
R8457 T27737 T27736 compound FVB,background
R8458 T27738 T27736 punct ),background
R8459 T27739 T27704 punct .,generated
R8460 T27741 T27742 nmod K14,cre
R8461 T27742 T27744 nmod cre,mice
R8462 T27743 T27742 punct -,cre
R8463 T27744 T27750 nsubjpass mice,crossed
R8464 T27745 T27742 punct ;,cre
R8465 T27746 T27742 appos ApcCKO,cre
R8466 T27747 T27746 punct /,ApcCKO
R8467 T27748 T27746 punct +,ApcCKO
R8468 T27749 T27744 amod male,mice
R8469 T27751 T27752 advmod thus,generated
R8470 T27752 T27744 acl generated,mice
R8471 T27753 T27750 auxpass were,crossed
R8472 T27754 T27750 advmod then,crossed
R8473 T27755 T27750 prep with,crossed
R8474 T27756 T27757 compound ApcCKO,CKO
R8475 T27757 T27759 compound CKO,females
R8476 T27758 T27757 punct /,CKO
R8477 T27759 T27755 pobj females,with
R8478 T27760 T27761 aux to,generate
R8479 T27761 T27750 advcl generate,crossed
R8480 T27762 T27763 amod homozygous,offspring
R8481 T27763 T27761 dobj offspring,generate
R8482 T27764 T27762 cc and,homozygous
R8483 T27765 T27762 conj heterozygous,homozygous
R8484 T27766 T27763 compound ApcCKO,offspring
R8485 T27767 T27768 preconj either,with
R8486 T27768 T27763 prep with,offspring
R8487 T27769 T27768 cc or,with
R8488 T27770 T27768 conj without,with
R8489 T27771 T27772 compound K14,cre
R8490 T27772 T27770 pobj cre,without
R8491 T27773 T27772 punct -,cre
R8492 T27774 T27750 punct .,crossed
R8493 T27776 T27777 det The,mice
R8494 T27777 T27778 nsubjpass mice,intercrossed
R8495 T27779 T27778 auxpass were,intercrossed
R8496 T27780 T27778 advmod thereafter,intercrossed
R8497 T27781 T27778 prep for,intercrossed
R8498 T27782 T27781 pobj maintenance,for
R8499 T27783 T27778 punct .,intercrossed
R8502 T28263 T28262 prep of,Genotyping
R8503 T28264 T28263 pobj mice,of
R8504 T28265 T28262 punct .,Genotyping
R8505 T28267 T28268 amod Genomic,DNA
R8506 T28268 T28269 nsubjpass DNA,genotyped
R8507 T28270 T28268 prep from,DNA
R8508 T28271 T28270 pobj tips,from
R8509 T28272 T28271 prep of,tips
R8510 T28273 T28274 compound mouse,tails
R8511 T28274 T28272 pobj tails,of
R8512 T28275 T28274 acl obtained,tails
R8513 T28276 T28275 prep at,obtained
R8514 T28277 T28278 punct ~,10
R8515 T28278 T28279 nummod 10,d
R8516 T28279 T28276 pobj d,at
R8517 T28280 T28279 prep of,d
R8518 T28281 T28280 pobj age,of
R8519 T28282 T28269 auxpass was,genotyped
R8520 T28283 T28269 prep in,genotyped
R8521 T28284 T28285 det a,reaction
R8522 T28285 T28283 pobj reaction,in
R8523 T28286 T28285 amod single,reaction
R8524 T28287 T28285 compound PCR,reaction
R8525 T28288 T28269 prep with,genotyped
R8526 T28289 T28290 det the,primers
R8527 T28290 T28288 pobj primers,with
R8528 T28291 T28290 amod following,primers
R8529 T28292 T28290 punct : ,primers
R8530 T28293 T28294 compound Apc,Int13F2
R8531 T28294 T28290 appos Int13F2,primers
R8532 T28295 T28294 punct -,Int13F2
R8533 T28296 T28297 punct (,GAGAAACCCTGTCTCGAAAAAA
R8534 T28297 T28294 parataxis GAGAAACCCTGTCTCGAAAAAA,Int13F2
R8535 T28298 T28297 punct ),GAGAAACCCTGTCTCGAAAAAA
R8536 T28299 T28294 cc and,Int13F2
R8537 T28300 T28301 compound Apc,Int13R2
R8538 T28301 T28294 conj Int13R2,Int13F2
R8539 T28302 T28301 punct -,Int13R2
R8540 T28303 T28304 punct (,AGTGCTGTTTCTATGAGTCAAC
R8541 T28304 T28301 parataxis AGTGCTGTTTCTATGAGTCAAC,Int13R2
R8542 T28305 T28304 punct ),AGTGCTGTTTCTATGAGTCAAC
R8543 T28306 T28269 punct ", ",genotyped
R8544 T28307 T28269 advcl resulting,genotyped
R8545 T28308 T28307 prep in,resulting
R8546 T28309 T28310 nummod 320,bp
R8547 T28310 T28312 nmod bp,products
R8548 T28311 T28310 punct -,bp
R8549 T28312 T28308 pobj products,in
R8550 T28313 T28310 cc and,bp
R8551 T28314 T28315 nummod 430,bp
R8552 T28315 T28310 conj bp,bp
R8553 T28316 T28315 punct -,bp
R8554 T28317 T28312 prep from,products
R8555 T28318 T28319 det the,allele
R8556 T28319 T28317 pobj allele,from
R8557 T28320 T28321 amod wild,type
R8558 T28321 T28319 nmod type,allele
R8559 T28322 T28321 punct -,type
R8560 T28323 T28321 cc and,type
R8561 T28324 T28325 amod conditional,ApcCKO
R8562 T28325 T28321 conj ApcCKO,type
R8563 T28326 T28307 punct ", ",resulting
R8564 T28327 T28307 advmod respectively,resulting
R8565 T28328 T28269 punct .,genotyped
R8566 T28330 T28331 prep For,resulted
R8567 T28332 T28333 det the,detection
R8568 T28333 T28330 pobj detection,For
R8569 T28334 T28333 prep of,detection
R8570 T28335 T28336 npadvmod Cre,mediated
R8571 T28336 T28338 amod mediated,allele
R8572 T28337 T28336 punct -,mediated
R8573 T28338 T28334 pobj allele,of
R8574 T28339 T28340 amod deleted,Apc
R8575 T28340 T28338 compound Apc,allele
R8576 T28341 T28331 punct ", ",resulted
R8577 T28342 T28331 nsubj ApcΔ580,resulted
R8578 T28343 T28342 punct ", ",ApcΔ580
R8579 T28344 T28345 det the,primer
R8580 T28345 T28342 appos primer,ApcΔ580
R8581 T28346 T28347 compound Apc,Int14R4
R8582 T28347 T28345 appos Int14R4,primer
R8583 T28348 T28347 punct -,Int14R4
R8584 T28349 T28350 punct (,TTGGCAGACTGTGTATATAAGC
R8585 T28350 T28345 parataxis TTGGCAGACTGTGTATATAAGC,primer
R8586 T28351 T28350 punct ),TTGGCAGACTGTGTATATAAGC
R8587 T28352 T28345 prep in,primer
R8588 T28353 T28352 pobj combination,in
R8589 T28354 T28353 prep with,combination
R8590 T28355 T28356 compound Apc,Int13F2
R8591 T28356 T28354 pobj Int13F2,with
R8592 T28357 T28356 punct -,Int13F2
R8593 T28358 T28331 prep in,resulted
R8594 T28359 T28360 nummod 500,bp
R8595 T28360 T28362 compound bp,product
R8596 T28361 T28360 punct -,bp
R8597 T28362 T28358 pobj product,in
R8598 T28363 T28331 punct .,resulted
R8599 T28365 T28366 compound Primers,F1
R8600 T28366 T28369 nsubjpass F1,used
R8601 T28367 T28366 compound Cre,F1
R8602 T28368 T28366 punct -,F1
R8603 T28370 T28371 punct (,TCCAATTTACTGACCGTACACC
R8604 T28371 T28366 parataxis TCCAATTTACTGACCGTACACC,F1
R8605 T28372 T28371 punct ),TCCAATTTACTGACCGTACACC
R8606 T28373 T28366 cc and,F1
R8607 T28374 T28375 compound Cre,R1
R8608 T28375 T28366 conj R1,F1
R8609 T28376 T28375 punct -,R1
R8610 T28377 T28378 punct (,CCGACGATGAAGCATGTTTAG
R8611 T28378 T28375 parataxis CCGACGATGAAGCATGTTTAG,R1
R8612 T28379 T28378 punct ),CCGACGATGAAGCATGTTTAG
R8613 T28380 T28369 auxpass were,used
R8614 T28381 T28369 prep for,used
R8615 T28382 T28381 pobj detection,for
R8616 T28383 T28382 prep of,detection
R8617 T28384 T28385 compound cre,transgene
R8618 T28385 T28383 pobj transgene,of
R8619 T28386 T28382 prep in,detection
R8620 T28387 T28388 det the,germline
R8621 T28388 T28386 pobj germline,in
R8622 T28389 T28369 punct ", ",used
R8623 T28390 T28369 advcl resulting,used
R8624 T28391 T28390 prep in,resulting
R8625 T28392 T28393 nummod 300,bp
R8626 T28393 T28395 compound bp,products
R8627 T28394 T28393 punct -,bp
R8628 T28395 T28391 pobj products,in
R8629 T28396 T28369 punct .,used
R8630 T28398 T28399 nsubjpass Amplification,performed
R8631 T28400 T28399 auxpass was,performed
R8632 T28401 T28399 prep in,performed
R8633 T28402 T28403 det a,volume
R8634 T28403 T28401 pobj volume,in
R8635 T28404 T28405 nummod 25,μl
R8636 T28405 T28403 compound μl,volume
R8637 T28406 T28405 punct -,μl
R8638 T28407 T28403 acl containing,volume
R8639 T28408 T28409 nummod 15,mM
R8640 T28409 T28410 compound mM,HCl
R8641 T28410 T28407 dobj HCl,containing
R8642 T28411 T28410 compound Tris,HCl
R8643 T28412 T28410 punct -,HCl
R8644 T28413 T28414 punct (,pH
R8645 T28414 T28410 parataxis pH,HCl
R8646 T28415 T28414 nummod 8.3,pH
R8647 T28416 T28414 punct ),pH
R8648 T28417 T28410 punct ", ",HCl
R8649 T28418 T28419 nummod 50,mM
R8650 T28419 T28420 compound mM,KCl
R8651 T28420 T28410 conj KCl,HCl
R8652 T28421 T28420 punct ", ",KCl
R8653 T28422 T28423 nummod 2.5,mM
R8654 T28423 T28424 compound mM,MgCl2
R8655 T28424 T28420 conj MgCl2,KCl
R8656 T28425 T28424 punct ", ",MgCl2
R8657 T28426 T28427 nummod 0.2,mM
R8658 T28427 T28428 compound mM,dNTP
R8659 T28428 T28424 conj dNTP,MgCl2
R8660 T28429 T28428 punct ", ",dNTP
R8661 T28430 T28431 nummod 0.2,μM
R8662 T28431 T28428 conj μM,dNTP
R8663 T28432 T28431 prep of,μM
R8664 T28433 T28434 det each,primer
R8665 T28434 T28432 pobj primer,of
R8666 T28435 T28431 punct ", ",μM
R8667 T28436 T28431 cc and,μM
R8668 T28437 T28438 nummod 1.25,U
R8669 T28438 T28431 conj U,μM
R8670 T28439 T28438 prep of,U
R8671 T28440 T28441 compound AmpliTaq,Gold
R8672 T28441 T28439 pobj Gold,of
R8673 T28442 T28443 punct (,Biosystems
R8674 T28443 T28441 parataxis Biosystems,Gold
R8675 T28444 T28443 compound Applied,Biosystems
R8676 T28445 T28443 punct ", ",Biosystems
R8677 T28446 T28447 compound Foster,City
R8678 T28447 T28443 npadvmod City,Biosystems
R8679 T28448 T28443 punct ", ",Biosystems
R8680 T28449 T28443 npadvmod California,Biosystems
R8681 T28450 T28443 punct ", ",Biosystems
R8682 T28451 T28452 compound United,States
R8683 T28452 T28443 npadvmod States,Biosystems
R8684 T28453 T28443 punct ),Biosystems
R8685 T28454 T28399 punct .,performed
R8686 T28456 T28457 det The,reactions
R8687 T28457 T28458 nsubjpass reactions,heated
R8688 T28459 T28458 auxpass were,heated
R8689 T28460 T28458 prep for,heated
R8690 T28461 T28462 nummod 10,min
R8691 T28462 T28460 pobj min,for
R8692 T28463 T28458 prep at,heated
R8693 T28464 T28465 nummod 94,°C
R8694 T28465 T28463 pobj °C,at
R8695 T28466 T28467 aux to,activate
R8696 T28467 T28458 advcl activate,heated
R8697 T28468 T28467 dep heat,activate
R8698 T28469 T28467 punct -,activate
R8699 T28470 T28471 det the,enzyme
R8700 T28471 T28467 dobj enzyme,activate
R8701 T28472 T28458 advcl followed,heated
R8702 T28473 T28472 agent by,followed
R8703 T28474 T28475 nummod 30,cycles
R8704 T28475 T28473 pobj cycles,by
R8705 T28476 T28475 compound PCR,cycles
R8706 T28477 T28475 prep at,cycles
R8707 T28478 T28479 nummod 94,°C
R8708 T28479 T28477 pobj °C,at
R8709 T28480 T28475 prep for,cycles
R8710 T28481 T28482 nummod 30,s
R8711 T28482 T28480 pobj s,for
R8712 T28483 T28475 punct ", ",cycles
R8713 T28484 T28485 nummod 58,°C
R8714 T28485 T28475 conj °C,cycles
R8715 T28486 T28485 prep for,°C
R8716 T28487 T28488 nummod 30,s
R8717 T28488 T28486 pobj s,for
R8718 T28489 T28485 punct ", ",°C
R8719 T28490 T28485 cc and,°C
R8720 T28491 T28492 nummod 72,°C
R8721 T28492 T28485 conj °C,°C
R8722 T28493 T28492 prep for,°C
R8723 T28494 T28495 nummod 45,s
R8724 T28495 T28493 pobj s,for
R8725 T28496 T28475 punct ", ",cycles
R8726 T28497 T28475 acl followed,cycles
R8727 T28498 T28497 agent by,followed
R8728 T28499 T28500 det the,extension
R8729 T28500 T28498 pobj extension,by
R8730 T28501 T28500 amod final,extension
R8731 T28502 T28500 prep for,extension
R8732 T28503 T28504 nummod 5,min
R8733 T28504 T28502 pobj min,for
R8734 T28505 T28500 prep at,extension
R8735 T28506 T28507 nummod 72,°C
R8736 T28507 T28505 pobj °C,at
R8737 T28508 T28458 punct .,heated
R8738 T28760 T28761 compound Skin,permeability
R8739 T28761 T28762 compound permeability,assay
R8740 T28763 T28762 punct .,assay
R8741 T28765 T28766 amod Unfixed,embryos
R8742 T28766 T28771 nsubjpass embryos,rinsed
R8743 T28767 T28765 cc and,Unfixed
R8744 T28768 T28769 advmod freshly,isolated
R8745 T28769 T28765 conj isolated,Unfixed
R8746 T28770 T28766 compound E18.5,embryos
R8747 T28772 T28771 auxpass were,rinsed
R8748 T28773 T28771 prep in,rinsed
R8749 T28774 T28773 pobj PBS,in
R8750 T28775 T28771 cc and,rinsed
R8751 T28776 T28777 advmod then,submerged
R8752 T28777 T28771 conj submerged,rinsed
R8753 T28778 T28777 prep in,submerged
R8754 T28779 T28780 compound X,gal
R8755 T28780 T28782 compound gal,mix
R8756 T28781 T28780 punct -,gal
R8757 T28782 T28778 pobj mix,in
R8758 T28783 T28782 compound reaction,mix
R8759 T28784 T28782 prep at,mix
R8760 T28785 T28784 pobj pH,at
R8761 T28786 T28785 nummod 4.5,pH
R8762 T28787 T28788 punct (,NaPO4
R8763 T28788 T28782 parataxis NaPO4,mix
R8764 T28789 T28790 nummod 100,mM
R8765 T28790 T28788 compound mM,NaPO4
R8766 T28791 T28788 punct ", ",NaPO4
R8767 T28792 T28793 nummod 1.3,mM
R8768 T28793 T28794 compound mM,MgCl2
R8769 T28794 T28788 conj MgCl2,NaPO4
R8770 T28795 T28794 punct ", ",MgCl2
R8771 T28796 T28797 nummod 3,mM
R8772 T28797 T28798 compound mM,K3Fe
R8773 T28798 T28794 conj K3Fe,MgCl2
R8774 T28799 T28800 punct (,CN
R8775 T28800 T28798 parataxis CN,K3Fe
R8776 T28801 T28800 punct ),CN
R8777 T28802 T28798 nummod 6,K3Fe
R8778 T28803 T28798 punct ", ",K3Fe
R8779 T28804 T28805 nummod 3,mM
R8780 T28805 T28806 compound mM,K4Fe
R8781 T28806 T28798 conj K4Fe,K3Fe
R8782 T28807 T28808 punct (,CN
R8783 T28808 T28806 parataxis CN,K4Fe
R8784 T28809 T28808 punct ),CN
R8785 T28810 T28806 nummod 6,K4Fe
R8786 T28811 T28806 punct ", ",K4Fe
R8787 T28812 T28806 cc and,K4Fe
R8788 T28813 T28814 nummod 1,mg
R8789 T28814 T28815 nmod mg,gal
R8790 T28815 T28806 conj gal,K4Fe
R8791 T28816 T28817 punct /,ml
R8792 T28817 T28814 prep ml,mg
R8793 T28818 T28815 compound X,gal
R8794 T28819 T28815 punct -,gal
R8795 T28820 T28815 punct ),gal
R8796 T28821 T28777 prep at,submerged
R8797 T28822 T28823 compound room,temperature
R8798 T28823 T28821 pobj temperature,at
R8799 T28824 T28777 advmod overnight,submerged
R8800 T28825 T28826 punct [,36
R8801 T28826 T28777 parataxis 36,submerged
R8802 T28827 T28826 punct ],36
R8803 T28828 T28771 punct .,rinsed
R8804 T28830 T28831 prep At,penetrates
R8805 T28832 T28833 det this,pH
R8806 T28833 T28830 pobj pH,At
R8807 T28834 T28831 prep in,penetrates
R8808 T28835 T28836 det the,absence
R8809 T28836 T28834 pobj absence,in
R8810 T28837 T28836 prep of,absence
R8811 T28838 T28839 amod epidermal,barrier
R8812 T28839 T28837 pobj barrier,of
R8813 T28840 T28831 punct ", ",penetrates
R8814 T28841 T28842 det the,solution
R8815 T28842 T28831 nsubj solution,penetrates
R8816 T28843 T28831 dobj epidermis,penetrates
R8817 T28844 T28831 cc and,penetrates
R8818 T28845 T28846 det an,activity
R8819 T28846 T28853 nsubj activity,catalyzes
R8820 T28847 T28846 amod endogenous,activity
R8821 T28848 T28849 amod β,galactosidase
R8822 T28849 T28851 npadvmod galactosidase,like
R8823 T28850 T28849 punct -,galactosidase
R8824 T28851 T28846 amod like,activity
R8825 T28852 T28851 punct –,like
R8826 T28853 T28831 conj catalyzes,penetrates
R8827 T28854 T28853 dobj production,catalyzes
R8828 T28855 T28854 prep of,production
R8829 T28856 T28857 det a,precipitate
R8830 T28857 T28855 pobj precipitate,of
R8831 T28858 T28857 amod blue,precipitate
R8832 T28859 T28831 punct .,penetrates
R8833 T28861 T28862 prep After,washed
R8834 T28863 T28861 pobj staining,After
R8835 T28864 T28862 punct ", ",washed
R8836 T28865 T28862 nsubjpass embryos,washed
R8837 T28866 T28862 auxpass were,washed
R8838 T28867 T28862 advmod twice,washed
R8839 T28868 T28862 prep in,washed
R8840 T28869 T28868 pobj PBS,in
R8841 T28870 T28862 punct ", ",washed
R8842 T28871 T28862 dep fixed,washed
R8843 T28872 T28871 advmod overnight,fixed
R8844 T28873 T28871 prep at,fixed
R8845 T28874 T28875 nummod 4,°C
R8846 T28875 T28873 pobj °C,at
R8847 T28876 T28871 prep in,fixed
R8848 T28877 T28878 nummod 4,%
R8849 T28878 T28879 compound %,paraformaldehyde
R8850 T28879 T28876 pobj paraformaldehyde,in
R8851 T28880 T28862 punct ", ",washed
R8852 T28881 T28862 cc and,washed
R8853 T28882 T28883 auxpass were,photographed
R8854 T28883 T28862 conj photographed,washed
R8855 T28884 T28883 advcl using,photographed
R8856 T28885 T28886 det a,camera
R8857 T28886 T28884 dobj camera,using
R8858 T28887 T28888 nummod 35,mm
R8859 T28888 T28886 nmod mm,camera
R8860 T28889 T28886 nmod Nikon,camera
R8861 T28890 T28886 amod digital,camera
R8862 T28891 T28862 punct .,washed
R8863 T29070 T29071 amod Skeletal,preparations
R8864 T29072 T29071 punct .,preparations
R8865 T29074 T29075 det The,bodies
R8866 T29075 T29079 nsubjpass bodies,placed
R8867 T29076 T29075 amod skinned,bodies
R8868 T29077 T29076 cc and,skinned
R8869 T29078 T29076 conj eviscerated,skinned
R8870 T29080 T29075 prep of,bodies
R8871 T29081 T29082 det the,mutants
R8872 T29082 T29080 pobj mutants,of
R8873 T29083 T29082 amod oldest,mutants
R8874 T29084 T29082 amod surviving,mutants
R8875 T29085 T29082 compound KA,mutants
R8876 T29086 T29087 punct (,P16
R8877 T29087 T29082 parataxis P16,mutants
R8878 T29088 T29089 punct –,P17
R8879 T29089 T29087 prep P17,P16
R8880 T29090 T29087 punct ),P16
R8881 T29091 T29082 cc and,mutants
R8882 T29092 T29093 poss their,littermates
R8883 T29093 T29082 conj littermates,mutants
R8884 T29094 T29095 npadvmod age,matched
R8885 T29095 T29093 amod matched,littermates
R8886 T29096 T29095 punct -,matched
R8887 T29097 T29079 auxpass were,placed
R8888 T29098 T29079 prep into,placed
R8889 T29099 T29100 nummod 1,%
R8890 T29100 T29101 compound %,hydroxide
R8891 T29101 T29098 pobj hydroxide,into
R8892 T29102 T29101 compound potassium,hydroxide
R8893 T29103 T29104 punct (,KOH
R8894 T29104 T29101 parataxis KOH,hydroxide
R8895 T29105 T29104 punct ),KOH
R8896 T29106 T29079 prep for,placed
R8897 T29107 T29108 nummod 5,d
R8898 T29108 T29106 pobj d,for
R8899 T29109 T29079 punct .,placed
R8900 T29111 T29112 det The,bodies
R8901 T29112 T29113 nsubjpass bodies,transferred
R8902 T29114 T29113 auxpass were,transferred
R8903 T29115 T29113 prep into,transferred
R8904 T29116 T29117 det a,solution
R8905 T29117 T29115 pobj solution,into
R8906 T29118 T29117 amod fresh,solution
R8907 T29119 T29117 prep of,solution
R8908 T29120 T29121 nummod 1,%
R8909 T29121 T29122 compound %,KOH
R8910 T29122 T29119 pobj KOH,of
R8911 T29123 T29117 acl containing,solution
R8912 T29124 T29125 det a,drops
R8913 T29125 T29123 dobj drops,containing
R8914 T29126 T29125 compound few,drops
R8915 T29127 T29125 prep of,drops
R8916 T29128 T29129 nummod 0.5,%
R8917 T29129 T29130 compound %,S
R8918 T29130 T29127 pobj S,of
R8919 T29131 T29130 compound alizarin,S
R8920 T29132 T29130 compound red,S
R8921 T29133 T29134 punct (,Sigma
R8922 T29134 T29130 parataxis Sigma,S
R8923 T29135 T29134 punct ", ",Sigma
R8924 T29136 T29137 compound St.,Louis
R8925 T29137 T29134 npadvmod Louis,Sigma
R8926 T29138 T29134 punct ", ",Sigma
R8927 T29139 T29134 npadvmod Missouri,Sigma
R8928 T29140 T29134 punct ", ",Sigma
R8929 T29141 T29142 compound United,States
R8930 T29142 T29134 npadvmod States,Sigma
R8931 T29143 T29134 punct ),Sigma
R8932 T29144 T29113 cc and,transferred
R8933 T29145 T29113 conj left,transferred
R8934 T29146 T29145 prep for,left
R8935 T29147 T29148 det another,d
R8936 T29148 T29146 pobj d,for
R8937 T29149 T29148 nummod 5,d
R8938 T29150 T29113 punct .,transferred
R8939 T29152 T29153 det The,bodies
R8940 T29153 T29155 nsubjpass bodies,stored
R8941 T29154 T29153 amod stained,bodies
R8942 T29156 T29155 auxpass were,stored
R8943 T29157 T29155 prep in,stored
R8944 T29158 T29157 pobj glycerin,in
R8945 T29159 T29155 cc and,stored
R8946 T29160 T29155 conj viewed,stored
R8947 T29161 T29160 prep under,viewed
R8948 T29162 T29163 det a,microscope
R8949 T29163 T29161 pobj microscope,under
R8950 T29164 T29163 compound dissection,microscope
R8951 T29165 T29155 punct .,stored
R8952 T29501 T29500 prep for,Analysis
R8953 T29502 T29503 npadvmod tissue,specific
R8954 T29503 T29505 amod specific,recombination
R8955 T29504 T29503 punct -,specific
R8956 T29505 T29501 pobj recombination,for
R8957 T29506 T29500 punct .,Analysis
R8958 T29508 T29509 compound Genotype,tissue
R8959 T29509 T29511 npadvmod tissue,specific
R8960 T29510 T29509 punct /,tissue
R8961 T29511 T29513 amod specific,recombination
R8962 T29512 T29511 punct -,specific
R8963 T29513 T29514 nsubjpass recombination,examined
R8964 T29515 T29513 prep of,recombination
R8965 T29516 T29517 det the,allele
R8966 T29517 T29515 pobj allele,of
R8967 T29518 T29517 amod conditional,allele
R8968 T29519 T29514 auxpass was,examined
R8969 T29520 T29514 prep by,examined
R8970 T29521 T29522 preconj both,PCR
R8971 T29522 T29520 pobj PCR,by
R8972 T29523 T29522 cc and,PCR
R8973 T29524 T29525 compound RT,PCR
R8974 T29525 T29522 conj PCR,PCR
R8975 T29526 T29525 punct -,PCR
R8976 T29527 T29514 punct .,examined
R8977 T29529 T29530 compound DNA,samples
R8978 T29530 T29531 nsubjpass samples,examined
R8979 T29532 T29530 acl extracted,samples
R8980 T29533 T29532 prep from,extracted
R8981 T29534 T29535 amod various,tissues
R8982 T29535 T29533 pobj tissues,from
R8983 T29536 T29535 acl collected,tissues
R8984 T29537 T29536 prep at,collected
R8985 T29538 T29539 det the,time
R8986 T29539 T29537 pobj time,at
R8987 T29540 T29539 prep of,time
R8988 T29541 T29540 pobj autopsy,of
R8989 T29542 T29531 auxpass were,examined
R8990 T29543 T29531 prep by,examined
R8991 T29544 T29543 pcomp genotyping,by
R8992 T29545 T29544 dobj PCR,genotyping
R8993 T29546 T29547 mark as,described
R8994 T29547 T29544 advcl described,genotyping
R8995 T29548 T29531 punct .,examined
R8996 T29550 T29551 nsubjpass RNA,examined
R8997 T29552 T29550 acl extracted,RNA
R8998 T29553 T29552 prep from,extracted
R8999 T29554 T29555 amod various,homogenates
R9000 T29555 T29553 pobj homogenates,from
R9001 T29556 T29555 compound tissue,homogenates
R9002 T29557 T29555 prep in,homogenates
R9003 T29558 T29559 compound Trizol,reagent
R9004 T29559 T29557 pobj reagent,in
R9005 T29560 T29551 auxpass were,examined
R9006 T29561 T29551 prep for,examined
R9007 T29562 T29561 pobj expression,for
R9008 T29563 T29562 prep of,expression
R9009 T29564 T29565 amod wild,type
R9010 T29565 T29567 nmod type,alleles
R9011 T29566 T29565 punct -,type
R9012 T29567 T29563 pobj alleles,of
R9013 T29568 T29565 cc and,type
R9014 T29569 T29570 amod truncated,Apc
R9015 T29570 T29565 conj Apc,type
R9016 T29571 T29551 prep by,examined
R9017 T29572 T29573 nmod SuperScript,PCR
R9018 T29573 T29571 pobj PCR,by
R9019 T29574 T29575 nummod One,Step
R9020 T29575 T29573 compound Step,PCR
R9021 T29576 T29575 punct -,Step
R9022 T29577 T29573 compound RT,PCR
R9023 T29578 T29573 punct -,PCR
R9024 T29579 T29573 prep with,PCR
R9025 T29580 T29581 compound Platinum,Taq
R9026 T29581 T29579 pobj Taq,with
R9027 T29582 T29583 punct (,Invitrogen
R9028 T29583 T29573 parataxis Invitrogen,PCR
R9029 T29584 T29583 punct ", ",Invitrogen
R9030 T29585 T29583 npadvmod Carlsbad,Invitrogen
R9031 T29586 T29583 punct ", ",Invitrogen
R9032 T29587 T29583 npadvmod California,Invitrogen
R9033 T29588 T29583 punct ", ",Invitrogen
R9034 T29589 T29590 compound United,States
R9035 T29590 T29583 npadvmod States,Invitrogen
R9036 T29591 T29583 punct ),Invitrogen
R9037 T29592 T29551 punct ", ",examined
R9038 T29593 T29551 advcl following,examined
R9039 T29594 T29595 poss manufacturer,protocol
R9040 T29595 T29593 dobj protocol,following
R9041 T29596 T29594 case 's,manufacturer
R9042 T29597 T29551 punct .,examined
R9043 T29599 T29600 advmod Approximately,ng
R9044 T29600 T29602 nsubjpass ng,transcribed
R9045 T29601 T29600 nummod 200,ng
R9046 T29603 T29600 prep of,ng
R9047 T29604 T29605 amod total,RNA
R9048 T29605 T29603 pobj RNA,of
R9049 T29606 T29605 prep from,RNA
R9050 T29607 T29608 det either,skin
R9051 T29608 T29606 pobj skin,from
R9052 T29609 T29608 punct ", ",skin
R9053 T29610 T29608 conj liver,skin
R9054 T29611 T29610 punct ", ",liver
R9055 T29612 T29610 cc or,liver
R9056 T29613 T29610 conj thymus,liver
R9057 T29614 T29608 prep from,skin
R9058 T29615 T29616 det each,genotype
R9059 T29616 T29614 pobj genotype,from
R9060 T29617 T29602 auxpass was,transcribed
R9061 T29618 T29602 advmod reverse,transcribed
R9062 T29619 T29602 punct -,transcribed
R9063 T29620 T29602 advcl using,transcribed
R9064 T29621 T29620 dobj primers,using
R9065 T29622 T29623 compound Apc,F546
R9066 T29623 T29621 appos F546,primers
R9067 T29624 T29623 punct -,F546
R9068 T29625 T29626 punct (,TGAGGAATTTGTCTTGGCGAG
R9069 T29626 T29623 parataxis TGAGGAATTTGTCTTGGCGAG,F546
R9070 T29627 T29626 punct ),TGAGGAATTTGTCTTGGCGAG
R9071 T29628 T29623 cc and,F546
R9072 T29629 T29630 compound Apc,R721
R9073 T29630 T29623 conj R721,F546
R9074 T29631 T29630 punct -,R721
R9075 T29632 T29633 punct (,GCACTTCCCATGGCAATCATT
R9076 T29633 T29630 parataxis GCACTTCCCATGGCAATCATT,R721
R9077 T29634 T29633 punct ),GCACTTCCCATGGCAATCATT
R9078 T29635 T29602 punct ", ",transcribed
R9079 T29636 T29602 advcl resulting,transcribed
R9080 T29637 T29636 prep in,resulting
R9081 T29638 T29639 nummod 528,bp
R9082 T29639 T29641 nmod bp,products
R9083 T29640 T29639 punct -,bp
R9084 T29641 T29637 pobj products,in
R9085 T29642 T29639 cc and,bp
R9086 T29643 T29644 nummod 313,bp
R9087 T29644 T29639 conj bp,bp
R9088 T29645 T29644 punct -,bp
R9089 T29646 T29641 prep from,products
R9090 T29647 T29648 det the,alleles
R9091 T29648 T29646 pobj alleles,from
R9092 T29649 T29650 amod wild,type
R9093 T29650 T29648 nmod type,alleles
R9094 T29651 T29650 punct -,type
R9095 T29652 T29650 punct /,type
R9096 T29653 T29650 appos ApcCKO,type
R9097 T29654 T29648 cc and,alleles
R9098 T29655 T29656 compound ApcΔ580,allele
R9099 T29656 T29648 conj allele,alleles
R9100 T29657 T29636 punct ", ",resulting
R9101 T29658 T29636 advmod respectively,resulting
R9102 T29659 T29602 punct .,transcribed
R9103 T29758 T29759 compound BrdU,labeling
R9104 T29760 T29759 punct .,labeling
R9105 T29762 T29763 nsubjpass Mice,injected
R9106 T29764 T29763 auxpass were,injected
R9107 T29765 T29763 advmod intraperitoneally,injected
R9108 T29766 T29763 prep with,injected
R9109 T29767 T29768 advmod approximately,50
R9110 T29768 T29769 nummod 50,μg
R9111 T29769 T29770 nmod μg,weight
R9112 T29770 T29766 pobj weight,with
R9113 T29771 T29772 punct /,g
R9114 T29772 T29769 prep g,μg
R9115 T29773 T29770 compound body,weight
R9116 T29774 T29770 prep of,weight
R9117 T29775 T29774 pobj BrdU,of
R9118 T29776 T29777 punct (,Sigma
R9119 T29777 T29775 parataxis Sigma,BrdU
R9120 T29778 T29777 punct ),Sigma
R9121 T29779 T29770 acl dissolved,weight
R9122 T29780 T29779 prep in,dissolved
R9123 T29781 T29780 pobj PBS,in
R9124 T29782 T29783 nummod 2,h
R9125 T29783 T29784 npadvmod h,before
R9126 T29784 T29763 prep before,injected
R9127 T29785 T29786 poss their,death
R9128 T29786 T29784 pobj death,before
R9129 T29787 T29763 punct .,injected
R9130 T29789 T29790 compound Tissue,samples
R9131 T29790 T29791 nsubj samples,fixed
R9132 T29792 T29791 aux were,fixed
R9133 T29793 T29791 prep in,fixed
R9134 T29794 T29793 pobj Bouin,in
R9135 T29795 T29794 case 's,Bouin
R9136 T29796 T29791 cc and,fixed
R9137 T29797 T29791 conj processed,fixed
R9138 T29798 T29799 mark as,described
R9139 T29799 T29791 advcl described,fixed
R9140 T29800 T29799 advmod below,described
R9141 T29801 T29791 punct .,fixed
R9147 T30449 T30450 amod Histological,analysis
R9148 T30451 T30449 cc and,Histological
R9149 T30452 T30449 conj immunochemical,Histological
R9150 T30453 T30450 punct .,analysis
R9151 T30455 T30456 amod Mutant,mice
R9152 T30456 T30457 nsubjpass mice,killed
R9153 T30458 T30456 cc and,mice
R9154 T30459 T30460 npadvmod age,matching
R9155 T30460 T30462 amod matching,littermates
R9156 T30461 T30460 punct -,matching
R9157 T30462 T30456 conj littermates,mice
R9158 T30463 T30457 auxpass were,killed
R9159 T30464 T30457 advmod humanely,killed
R9160 T30465 T30457 prep at,killed
R9161 T30466 T30467 amod various,ages
R9162 T30467 T30465 pobj ages,at
R9163 T30468 T30457 prep by,killed
R9164 T30469 T30470 compound CO2,inhalation
R9165 T30470 T30468 pobj inhalation,by
R9166 T30471 T30457 punct .,killed
R9167 T30473 T30474 nsubjpass Mice,skinned
R9168 T30475 T30474 auxpass were,skinned
R9169 T30476 T30474 cc and,skinned
R9170 T30477 T30478 nsubj pieces,frozen
R9171 T30478 T30474 conj frozen,skinned
R9172 T30479 T30477 prep of,pieces
R9173 T30480 T30479 pobj skin,of
R9174 T30481 T30478 aux were,frozen
R9175 T30482 T30478 preconj either,frozen
R9176 T30483 T30478 dep snap,frozen
R9177 T30484 T30478 punct -,frozen
R9178 T30485 T30478 prep in,frozen
R9179 T30486 T30487 amod liquid,nitrogen
R9180 T30487 T30485 pobj nitrogen,in
R9181 T30488 T30478 cc or,frozen
R9182 T30489 T30490 advmod immediately,homogenized
R9183 T30490 T30478 conj homogenized,frozen
R9184 T30491 T30490 prep in,homogenized
R9185 T30492 T30493 compound Trizol,reagent
R9186 T30493 T30491 pobj reagent,in
R9187 T30494 T30478 cc and,frozen
R9188 T30495 T30478 conj stored,frozen
R9189 T30496 T30495 prep at,stored
R9190 T30497 T30498 punct −,80
R9191 T30498 T30499 nummod 80,°C
R9192 T30499 T30496 pobj °C,at
R9193 T30500 T30495 prep until,stored
R9194 T30501 T30502 amod molecular,analysis
R9195 T30502 T30500 pobj analysis,until
R9196 T30503 T30495 punct ", ",stored
R9197 T30504 T30495 cc or,stored
R9198 T30505 T30495 conj fixed,stored
R9199 T30506 T30505 oprd flat,fixed
R9200 T30507 T30505 prep on,fixed
R9201 T30508 T30509 det a,piece
R9202 T30509 T30507 pobj piece,on
R9203 T30510 T30509 prep of,piece
R9204 T30511 T30512 compound paper,towel
R9205 T30512 T30510 pobj towel,of
R9206 T30513 T30505 prep in,fixed
R9207 T30514 T30515 poss Bouin,solution
R9208 T30515 T30513 pobj solution,in
R9209 T30516 T30514 case 's,Bouin
R9210 T30517 T30505 prep for,fixed
R9211 T30518 T30519 amod histological,examinations
R9212 T30519 T30517 pobj examinations,for
R9213 T30520 T30518 cc and,histological
R9214 T30521 T30518 conj immunohistochemical,histological
R9215 T30522 T30478 punct .,frozen
R9216 T30524 T30525 det The,mice
R9217 T30525 T30526 nsubjpass mice,dissected
R9218 T30527 T30526 auxpass were,dissected
R9219 T30528 T30526 advmod then,dissected
R9220 T30529 T30526 prep for,dissected
R9221 T30530 T30531 amod gross,examination
R9222 T30531 T30529 pobj examination,for
R9223 T30532 T30526 punct ", ",dissected
R9224 T30533 T30534 amod various,tissues
R9225 T30534 T30535 nsubjpass tissues,collected
R9226 T30535 T30526 conj collected,dissected
R9227 T30536 T30535 auxpass were,collected
R9228 T30537 T30535 advmod similarly,collected
R9229 T30538 T30535 prep for,collected
R9230 T30539 T30540 amod future,analyses
R9231 T30540 T30538 pobj analyses,for
R9232 T30541 T30540 amod molecular,analyses
R9233 T30542 T30535 punct ", ",collected
R9234 T30543 T30535 cc and,collected
R9235 T30544 T30545 advmod then,fixed
R9236 T30545 T30535 conj fixed,collected
R9237 T30546 T30547 det the,body
R9238 T30547 T30545 nsubjpass body,fixed
R9239 T30548 T30547 amod whole,body
R9240 T30549 T30545 auxpass was,fixed
R9241 T30550 T30545 prep in,fixed
R9242 T30551 T30552 poss Bouin,solution
R9243 T30552 T30550 pobj solution,in
R9244 T30553 T30551 case 's,Bouin
R9245 T30554 T30545 punct .,fixed
R9246 T30556 T30557 det The,samples
R9247 T30557 T30558 nsubjpass samples,submitted
R9248 T30559 T30558 auxpass were,submitted
R9249 T30560 T30558 advmod then,submitted
R9250 T30561 T30558 prep to,submitted
R9251 T30562 T30563 compound Rodent,Core
R9252 T30563 T30561 pobj Core,to
R9253 T30564 T30563 compound Histopathological,Core
R9254 T30565 T30558 prep for,submitted
R9255 T30566 T30565 pobj processing,for
R9256 T30567 T30566 cc and,processing
R9257 T30568 T30569 amod histopathological,examinations
R9258 T30569 T30566 conj examinations,processing
R9259 T30570 T30558 punct .,submitted
R9260 T30572 T30573 prep For,deparafinized
R9261 T30574 T30572 pobj immunohistochemistry,For
R9262 T30575 T30573 punct ", ",deparafinized
R9263 T30576 T30577 nummod 5,μm
R9264 T30577 T30579 nmod μm,sections
R9265 T30578 T30577 punct -,μm
R9266 T30579 T30573 nsubjpass sections,deparafinized
R9267 T30580 T30581 npadvmod paraffin,embedded
R9268 T30581 T30579 amod embedded,sections
R9269 T30582 T30581 punct -,embedded
R9270 T30583 T30579 compound tissue,sections
R9271 T30584 T30573 auxpass were,deparafinized
R9272 T30585 T30573 prep in,deparafinized
R9273 T30586 T30585 pobj xylene,in
R9274 T30587 T30573 punct ", ",deparafinized
R9275 T30588 T30573 advcl followed,deparafinized
R9276 T30589 T30588 agent by,followed
R9277 T30590 T30591 compound alcohol,rehydration
R9278 T30591 T30589 pobj rehydration,by
R9279 T30592 T30573 punct .,deparafinized
R9280 T30594 T30595 prep After,rinsed
R9281 T30596 T30594 pcomp quenching,After
R9282 T30597 T30598 amod endogenous,peroxidases
R9283 T30598 T30596 dobj peroxidases,quenching
R9284 T30599 T30596 prep in,quenching
R9285 T30600 T30601 nummod 3,%
R9286 T30601 T30602 compound %,H2O2
R9287 T30602 T30599 pobj H2O2,in
R9288 T30603 T30596 prep in,quenching
R9289 T30604 T30603 pobj methanol,in
R9290 T30605 T30595 punct ", ",rinsed
R9291 T30606 T30607 det the,slides
R9292 T30607 T30595 nsubjpass slides,rinsed
R9293 T30608 T30595 auxpass were,rinsed
R9294 T30609 T30595 prep in,rinsed
R9295 T30610 T30611 amod distilled,water
R9296 T30611 T30609 pobj water,in
R9297 T30612 T30595 punct ", ",rinsed
R9298 T30613 T30595 cc and,rinsed
R9299 T30614 T30615 det an,step
R9300 T30615 T30618 nsubjpass step,carried
R9301 T30616 T30615 compound antigen,step
R9302 T30617 T30615 compound retrieval,step
R9303 T30618 T30595 conj carried,rinsed
R9304 T30619 T30618 auxpass was,carried
R9305 T30620 T30618 prt out,carried
R9306 T30621 T30618 prep in,carried
R9307 T30622 T30623 det a,microwave
R9308 T30623 T30621 pobj microwave,in
R9309 T30624 T30623 amod oven,microwave
R9310 T30625 T30618 prep for,carried
R9311 T30626 T30627 det a,total
R9312 T30627 T30625 pobj total,for
R9313 T30628 T30627 prep of,total
R9314 T30629 T30630 nummod 10,min
R9315 T30630 T30628 pobj min,of
R9316 T30631 T30618 prep in,carried
R9317 T30632 T30633 amod preheated,buffer
R9318 T30633 T30631 pobj buffer,in
R9319 T30634 T30633 compound citrate,buffer
R9320 T30635 T30636 punct (,pH
R9321 T30636 T30633 parataxis pH,buffer
R9322 T30637 T30636 nummod 6.0,pH
R9323 T30638 T30636 punct ),pH
R9324 T30639 T30595 punct .,rinsed
R9325 T30641 T30642 det The,slides
R9326 T30642 T30643 nsubjpass slides,incubated
R9327 T30644 T30643 auxpass were,incubated
R9328 T30645 T30643 advmod then,incubated
R9329 T30646 T30643 prep with,incubated
R9330 T30647 T30648 amod primary,antibodies
R9331 T30648 T30646 pobj antibodies,with
R9332 T30649 T30643 prep at,incubated
R9333 T30650 T30651 compound room,temperature
R9334 T30651 T30649 pobj temperature,at
R9335 T30652 T30643 advmod overnight,incubated
R9336 T30653 T30643 punct .,incubated
R9337 T30655 T30656 nsubj Antibodies,were
R9338 T30657 T30655 acl used,Antibodies
R9339 T30658 T30659 compound β,catenin
R9340 T30659 T30656 attr catenin,were
R9341 T30660 T30659 punct -,catenin
R9342 T30661 T30662 punct (,Lab
R9343 T30662 T30659 parataxis Lab,catenin
R9344 T30663 T30662 compound BD,Lab
R9345 T30664 T30662 compound Transduction,Lab
R9346 T30665 T30662 punct ", ",Lab
R9347 T30666 T30667 compound San,Diego
R9348 T30667 T30662 npadvmod Diego,Lab
R9349 T30668 T30662 punct ", ",Lab
R9350 T30669 T30662 npadvmod California,Lab
R9351 T30670 T30662 punct ", ",Lab
R9352 T30671 T30672 compound United,States
R9353 T30672 T30662 npadvmod States,Lab
R9354 T30673 T30662 punct ),Lab
R9355 T30674 T30659 punct ", ",catenin
R9356 T30675 T30676 nmod keratins,14
R9357 T30676 T30659 conj 14,catenin
R9358 T30677 T30676 nummod 1,14
R9359 T30678 T30676 punct ", ",14
R9360 T30679 T30676 nummod 5,14
R9361 T30680 T30676 punct ", ",14
R9362 T30681 T30676 nummod 6,14
R9363 T30682 T30676 punct ", ",14
R9364 T30683 T30676 punct ", ",14
R9365 T30684 T30676 conj involucrin,14
R9366 T30685 T30684 punct ", ",involucrin
R9367 T30686 T30684 conj loricrin,involucrin
R9368 T30687 T30688 punct (,Covance
R9369 T30688 T30686 parataxis Covance,loricrin
R9370 T30689 T30688 punct ", ",Covance
R9371 T30690 T30688 npadvmod Berkeley,Covance
R9372 T30691 T30688 punct ", ",Covance
R9373 T30692 T30688 npadvmod California,Covance
R9374 T30693 T30688 punct ", ",Covance
R9375 T30694 T30695 compound United,States
R9376 T30695 T30688 npadvmod States,Covance
R9377 T30696 T30688 punct ),Covance
R9378 T30697 T30686 punct ", ",loricrin
R9379 T30698 T30686 conj keratin,loricrin
R9380 T30699 T30698 nummod 8,keratin
R9381 T30700 T30701 punct (,Abcam
R9382 T30701 T30698 parataxis Abcam,keratin
R9383 T30702 T30701 punct ", ",Abcam
R9384 T30703 T30701 npadvmod Cambridge,Abcam
R9385 T30704 T30701 punct ", ",Abcam
R9386 T30705 T30706 compound United,Kingdom
R9387 T30706 T30701 npadvmod Kingdom,Abcam
R9388 T30707 T30701 punct ),Abcam
R9389 T30708 T30698 punct ", ",keratin
R9390 T30709 T30698 conj Ki67,keratin
R9391 T30710 T30711 punct (,Laboratories
R9392 T30711 T30709 parataxis Laboratories,Ki67
R9393 T30712 T30711 compound Vector,Laboratories
R9394 T30713 T30711 punct ", ",Laboratories
R9395 T30714 T30711 npadvmod Burlingame,Laboratories
R9396 T30715 T30711 punct ", ",Laboratories
R9397 T30716 T30711 npadvmod California,Laboratories
R9398 T30717 T30711 punct ", ",Laboratories
R9399 T30718 T30719 compound United,States
R9400 T30719 T30711 npadvmod States,Laboratories
R9401 T30720 T30711 punct ),Laboratories
R9402 T30721 T30709 cc and,Ki67
R9403 T30722 T30709 conj BrdU,Ki67
R9404 T30723 T30724 punct (,Roche
R9405 T30724 T30722 parataxis Roche,BrdU
R9406 T30725 T30724 punct ),Roche
R9407 T30726 T30656 punct .,were
R9408 T30728 T30729 amod Biotinylated,antibodies
R9409 T30729 T30731 nsubjpass antibodies,used
R9410 T30730 T30729 amod secondary,antibodies
R9411 T30732 T30733 punct (,ImmunoResearch
R9412 T30733 T30729 parataxis ImmunoResearch,antibodies
R9413 T30734 T30735 npadvmod donkey,anti-rabbit
R9414 T30735 T30736 amod anti-rabbit,IgG
R9415 T30736 T30733 dep IgG,ImmunoResearch
R9416 T30737 T30735 cc and,anti-rabbit
R9417 T30738 T30739 npadvmod goat,anti-mouse
R9418 T30739 T30735 conj anti-mouse,anti-rabbit
R9419 T30740 T30736 punct ", ",IgG
R9420 T30741 T30736 npadvmod 1,IgG
R9421 T30742 T30743 punct :,250
R9422 T30743 T30741 prep 250,1
R9423 T30744 T30733 punct ;,ImmunoResearch
R9424 T30745 T30733 compound Jackson,ImmunoResearch
R9425 T30746 T30733 punct ", ",ImmunoResearch
R9426 T30747 T30748 compound West,Grove
R9427 T30748 T30733 npadvmod Grove,ImmunoResearch
R9428 T30749 T30733 punct ", ",ImmunoResearch
R9429 T30750 T30733 npadvmod Pennsylvania,ImmunoResearch
R9430 T30751 T30733 punct ", ",ImmunoResearch
R9431 T30752 T30753 compound United,States
R9432 T30753 T30733 npadvmod States,ImmunoResearch
R9433 T30754 T30733 punct ),ImmunoResearch
R9434 T30755 T30729 punct ", ",antibodies
R9435 T30756 T30729 acl followed,antibodies
R9436 T30757 T30756 agent by,followed
R9437 T30758 T30759 det the,kit
R9438 T30759 T30757 pobj kit,by
R9439 T30760 T30759 compound Vectastain,kit
R9440 T30761 T30759 compound Elite,kit
R9441 T30762 T30759 compound ABC,kit
R9442 T30763 T30764 punct (,Laboratories
R9443 T30764 T30759 parataxis Laboratories,kit
R9444 T30765 T30764 compound Vector,Laboratories
R9445 T30766 T30764 punct ),Laboratories
R9446 T30767 T30731 auxpass were,used
R9447 T30768 T30731 prep for,used
R9448 T30769 T30768 pobj detection,for
R9449 T30770 T30731 punct .,used
R9450 T30772 T30773 det The,slides
R9451 T30773 T30774 nsubjpass slides,stained
R9452 T30775 T30774 auxpass were,stained
R9453 T30776 T30774 prep with,stained
R9454 T30777 T30776 pobj DAB,with
R9455 T30778 T30774 cc and,stained
R9456 T30779 T30774 conj counterstained,stained
R9457 T30780 T30779 prep with,counterstained
R9458 T30781 T30782 poss Mayer,hematoxylin
R9459 T30782 T30780 pobj hematoxylin,with
R9460 T30783 T30781 case 's,Mayer
R9461 T30784 T30774 punct .,stained
R9462 T30900 T30901 advmod In,situ
R9463 T30901 T30902 amod situ,hybridization
R9464 T30903 T30902 punct .,hybridization
R9465 T30905 T30906 compound Section,ISH
R9466 T30906 T30907 nsubjpass ISH,performed
R9467 T30908 T30906 acl using,ISH
R9468 T30909 T30910 compound rat,probe
R9469 T30910 T30908 dobj probe,using
R9470 T30911 T30910 compound Shh,probe
R9471 T30912 T30913 punct [,37
R9472 T30913 T30908 parataxis 37,using
R9473 T30914 T30913 punct ],37
R9474 T30915 T30906 cc and,ISH
R9475 T30916 T30917 amod whole,mount
R9476 T30917 T30919 compound mount,ISH
R9477 T30918 T30917 punct -,mount
R9478 T30919 T30906 conj ISH,ISH
R9479 T30920 T30919 acl using,ISH
R9480 T30921 T30922 compound β,catenin
R9481 T30922 T30924 compound catenin,probe
R9482 T30923 T30922 punct -,catenin
R9483 T30924 T30920 dobj probe,using
R9484 T30925 T30926 punct [,38
R9485 T30926 T30920 parataxis 38,using
R9486 T30927 T30926 punct ],38
R9487 T30928 T30907 auxpass were,performed
R9488 T30929 T30930 mark as,described
R9489 T30930 T30907 advcl described,performed
R9490 T30931 T30930 advmod previously,described
R9491 T30932 T30933 punct [,40
R9492 T30933 T30907 parataxis 40,performed
R9493 T30934 T30933 nummod 39,40
R9494 T30935 T30933 punct ",",40
R9495 T30936 T30933 punct ],40
R9496 T30937 T30907 punct .,performed
R9497 T30939 T30940 nsubjpass Riboprobes,detected
R9498 T30941 T30939 acl labeled,Riboprobes
R9499 T30942 T30941 prep with,labeled
R9500 T30943 T30942 pobj DIG,with
R9501 T30944 T30940 auxpass were,detected
R9502 T30945 T30940 prep with,detected
R9503 T30946 T30947 compound BM,purple
R9504 T30947 T30948 compound purple,solution
R9505 T30948 T30945 pobj solution,with
R9506 T30949 T30950 compound AP,substrate
R9507 T30950 T30948 compound substrate,solution
R9508 T30951 T30948 compound precipitation,solution
R9509 T30952 T30953 punct (,Roche
R9510 T30953 T30948 parataxis Roche,solution
R9511 T30954 T30953 punct ),Roche
R9512 T30955 T30940 punct .,detected
R89 T660 T658 pobj promoter,of

2_test

Id Subject Object Predicate Lexical cue
17002498-7753829-85593496 5162-5163 7753829 denotes 7
17002498-7576992-85593496 5162-5163 7576992 denotes 7
17002498-15372092-85593490 2985-2986 15372092 denotes 1
17002498-15473844-85593491 3743-3744 15473844 denotes 2
17002498-12646874-85593492 3745-3746 12646874 denotes 3
17002498-8861899-85593493 4175-4176 8861899 denotes 4
17002498-1651174-85593494 4177-4178 1651174 denotes 5
17002498-16454848-85593495 4470-4471 16454848 denotes 6
17002498-9054624-85593496 5162-5163 9054624 denotes 7
17002498-8090754-85593496 5162-5163 8090754 denotes 7
17002498-9054624-85593497 5284-5285 9054624 denotes 7
17002498-7753829-85593497 5284-5285 7753829 denotes 7
17002498-7576992-85593497 5284-5285 7576992 denotes 7
17002498-8090754-85593497 5284-5285 8090754 denotes 7
17002498-7753829-85593498 5439-5440 7753829 denotes 8
17002498-12645927-85593499 5441-5443 12645927 denotes 11
17002498-11352566-85593500 7019-7021 11352566 denotes 12
17002498-12618378-85593501 7022-7024 12618378 denotes 13
17002498-11352566-85593502 7271-7273 11352566 denotes 12
17002498-12618378-85593503 7274-7276 12618378 denotes 13
17002498-15502862-85593504 10381-10383 15502862 denotes 14
17002498-7638196-85593505 11863-11865 7638196 denotes 15
17002498-11694875-85593506 11930-11932 11694875 denotes 16
17002498-15083518-85593507 12143-12145 15083518 denotes 17
17002498-6155214-85593508 12518-12520 6155214 denotes 18
17002498-7525178-85593509 12649-12651 7525178 denotes 19
17002498-8982454-85593510 12766-12768 8982454 denotes 20
17002498-9502735-85593511 15396-15398 9502735 denotes 21
17002498-12913119-85593512 21312-21314 12913119 denotes 22
17002498-12756224-85593513 21315-21317 12756224 denotes 23
17002498-12913119-85593514 21799-21801 12913119 denotes 22
17002498-11694875-85593515 30904-30906 11694875 denotes 16
17002498-8861899-85593516 37509-37510 8861899 denotes 4
17002498-1651174-85593517 37511-37512 1651174 denotes 5
17002498-16454848-85593518 38059-38060 16454848 denotes 6
17002498-11841536-85593519 39326-39328 11841536 denotes 24
17002498-9845363-85593520 39708-39710 9845363 denotes 25
17002498-10409498-85593520 39708-39710 10409498 denotes 25
17002498-7537238-85593520 39708-39710 7537238 denotes 25
17002498-11371349-85593521 39948-39950 11371349 denotes 28
17002498-12015971-85593521 39948-39950 12015971 denotes 28
17002498-7958926-85593521 39948-39950 7958926 denotes 28
17002498-9845363-85593522 40992-40994 9845363 denotes 25
17002498-7537238-85593523 41026-41028 7537238 denotes 27
17002498-7525178-85593524 41803-41805 7525178 denotes 19
17002498-8990189-85593525 41806-41808 8990189 denotes 31
17002498-11694875-85593526 42443-42445 11694875 denotes 16
17002498-7537238-85593527 44392-44394 7537238 denotes 27
17002498-12015971-85593528 45728-45730 12015971 denotes 29
17002498-7958926-85593529 45731-45733 7958926 denotes 30
17002498-9751749-85593530 46766-46768 9751749 denotes 32
17002498-16025118-85593531 49756-49758 16025118 denotes 33
17002498-16454848-85593532 50130-50131 16454848 denotes 6
17002498-11352566-85593533 51203-51205 11352566 denotes 12
17002498-12618378-85593534 51206-51208 12618378 denotes 13
17002498-7638196-85593535 51644-51646 7638196 denotes 15
17002498-10835623-85593536 52390-52392 10835623 denotes 34
17002498-8650183-85593537 52803-52805 8650183 denotes 35
17002498-11923212-85593538 54795-54797 11923212 denotes 36
17002498-15668330-85593539 58501-58503 15668330 denotes 37
17002498-11973284-85593540 58548-58550 11973284 denotes 38
17002498-9925646-85593541 58592-58594 9925646 denotes 39
17002498-8269518-85593542 58595-58597 8269518 denotes 40
T4265 2985-2986 15372092 denotes 1
T35749 3743-3744 15473844 denotes 2
T93568 3745-3746 12646874 denotes 3
T18617 4175-4176 8861899 denotes 4
T46649 4177-4178 1651174 denotes 5
T91666 4470-4471 16454848 denotes 6
T45080 5162-5163 9054624 denotes 7
T40102 5162-5163 7753829 denotes 7
T88630 5162-5163 7576992 denotes 7
T58268 5162-5163 8090754 denotes 7
T41070 5284-5285 9054624 denotes 7
T43862 5284-5285 7753829 denotes 7
T10199 5284-5285 7576992 denotes 7
T88104 5284-5285 8090754 denotes 7
T81088 5439-5440 7753829 denotes 8
T78076 5441-5443 12645927 denotes 11
T44384 7019-7021 11352566 denotes 12
T16891 7022-7024 12618378 denotes 13
T61261 7271-7273 11352566 denotes 12
T27200 7274-7276 12618378 denotes 13
T47394 10381-10383 15502862 denotes 14
T13682 11863-11865 7638196 denotes 15
T44814 11930-11932 11694875 denotes 16
T95436 12143-12145 15083518 denotes 17
T63013 12518-12520 6155214 denotes 18
T6017 12649-12651 7525178 denotes 19
T84320 12766-12768 8982454 denotes 20
T96575 15396-15398 9502735 denotes 21
T94634 21312-21314 12913119 denotes 22
T66758 21315-21317 12756224 denotes 23
T12681 21799-21801 12913119 denotes 22
T49808 30904-30906 11694875 denotes 16
T99165 37509-37510 8861899 denotes 4
T77251 37511-37512 1651174 denotes 5
T6760 38059-38060 16454848 denotes 6
T58138 39326-39328 11841536 denotes 24
T2579 39708-39710 9845363 denotes 25
T26992 39708-39710 10409498 denotes 25
T7229 39708-39710 7537238 denotes 25
T24052 39948-39950 11371349 denotes 28
T27200 39948-39950 12015971 denotes 28
T60441 39948-39950 7958926 denotes 28
T55311 40992-40994 9845363 denotes 25
T47275 41026-41028 7537238 denotes 27
T44354 41803-41805 7525178 denotes 19
T70725 41806-41808 8990189 denotes 31
T26365 42443-42445 11694875 denotes 16
T95890 44392-44394 7537238 denotes 27
T41351 45728-45730 12015971 denotes 29
T13746 45731-45733 7958926 denotes 30
T31625 46766-46768 9751749 denotes 32
T47956 49756-49758 16025118 denotes 33
T48461 50130-50131 16454848 denotes 6
T46410 51203-51205 11352566 denotes 12
T7670 51206-51208 12618378 denotes 13
T61691 51644-51646 7638196 denotes 15
T25344 52390-52392 10835623 denotes 34
T57111 52803-52805 8650183 denotes 35
T84581 54795-54797 11923212 denotes 36
T47766 58501-58503 15668330 denotes 37
T50743 58548-58550 11973284 denotes 38
T66678 58592-58594 9925646 denotes 39
T62429 58595-58597 8269518 denotes 40