Id |
Subject |
Object |
Predicate |
Lexical cue |
T4597 |
0-10 |
NN |
denotes |
Generation |
T4598 |
11-13 |
IN |
denotes |
of |
T4599 |
14-17 |
DT |
denotes |
the |
T4600 |
37-41 |
NNS |
denotes |
Mice |
T4601 |
18-24 |
NN |
denotes |
ApcCKO |
T4602 |
25-28 |
CC |
denotes |
and |
T4603 |
29-36 |
NN |
denotes |
ApcΔ580 |
T4604 |
41-208 |
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 |
42-44 |
TO |
denotes |
To |
T4606 |
45-56 |
VB |
denotes |
investigate |
T4607 |
119-123 |
VBD |
denotes |
used |
T4608 |
57-60 |
DT |
denotes |
the |
T4609 |
61-65 |
NN |
denotes |
role |
T4610 |
66-68 |
IN |
denotes |
of |
T4611 |
69-72 |
NN |
denotes |
Apc |
T4612 |
73-75 |
IN |
denotes |
in |
T4613 |
76-87 |
NN |
denotes |
development |
T4614 |
88-90 |
IN |
denotes |
of |
T4615 |
91-95 |
NN |
denotes |
skin |
T4616 |
96-99 |
CC |
denotes |
and |
T4617 |
100-103 |
PRP$ |
denotes |
its |
T4618 |
104-114 |
NNS |
denotes |
appendages |
T4619 |
114-116 |
, |
denotes |
, |
T4620 |
116-118 |
PRP |
denotes |
we |
T4621 |
124-127 |
DT |
denotes |
the |
T4622 |
137-147 |
NN |
denotes |
technology |
T4623 |
128-131 |
NN |
denotes |
Cre |
T4624 |
132-136 |
NN |
denotes |
loxP |
T4625 |
131-132 |
HYPH |
denotes |
/ |
T4626 |
148-150 |
TO |
denotes |
to |
T4627 |
151-160 |
VB |
denotes |
introduce |
T4628 |
161-162 |
DT |
denotes |
a |
T4629 |
175-183 |
NN |
denotes |
mutation |
T4630 |
163-174 |
JJ |
denotes |
conditional |
T4631 |
184-186 |
IN |
denotes |
of |
T4632 |
187-190 |
DT |
denotes |
the |
T4633 |
195-199 |
NN |
denotes |
gene |
T4634 |
191-194 |
NN |
denotes |
Apc |
T4635 |
200-202 |
IN |
denotes |
in |
T4636 |
203-207 |
NNS |
denotes |
mice |
T4637 |
207-208 |
. |
denotes |
. |
T4638 |
208-508 |
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 |
209-211 |
PRP |
denotes |
We |
T4640 |
212-223 |
VBD |
denotes |
constructed |
T4641 |
224-233 |
JJ |
denotes |
embryonic |
T4642 |
234-238 |
NN |
denotes |
stem |
T4643 |
244-249 |
NNS |
denotes |
cells |
T4644 |
239-240 |
-LRB- |
denotes |
( |
T4645 |
240-242 |
NN |
denotes |
ES |
T4646 |
242-243 |
-RRB- |
denotes |
) |
T4647 |
250-253 |
CC |
denotes |
and |
T4648 |
254-258 |
NNS |
denotes |
mice |
T4649 |
259-267 |
VBG |
denotes |
carrying |
T4650 |
268-270 |
DT |
denotes |
an |
T4651 |
275-281 |
NN |
denotes |
allele |
T4652 |
271-274 |
NN |
denotes |
Apc |
T4653 |
282-291 |
VBG |
denotes |
harboring |
T4654 |
292-296 |
CC |
denotes |
both |
T4655 |
299-303 |
NN |
denotes |
pair |
T4656 |
297-298 |
DT |
denotes |
a |
T4657 |
304-306 |
IN |
denotes |
of |
T4658 |
307-311 |
NN |
denotes |
loxP |
T4659 |
312-317 |
NNS |
denotes |
sites |
T4660 |
318-326 |
VBG |
denotes |
flanking |
T4661 |
327-330 |
NN |
denotes |
Apc |
T4662 |
331-335 |
NN |
denotes |
exon |
T4663 |
336-338 |
CD |
denotes |
14 |
T4664 |
339-342 |
CC |
denotes |
and |
T4665 |
343-344 |
DT |
denotes |
a |
T4666 |
345-349 |
NN |
denotes |
pair |
T4667 |
350-352 |
IN |
denotes |
of |
T4668 |
353-356 |
NN |
denotes |
FLP |
T4669 |
369-375 |
NN |
denotes |
target |
T4670 |
357-368 |
NN |
denotes |
recognition |
T4671 |
382-387 |
NNS |
denotes |
sites |
T4672 |
376-377 |
-LRB- |
denotes |
( |
T4673 |
377-380 |
NN |
denotes |
FRT |
T4674 |
380-381 |
-RRB- |
denotes |
) |
T4675 |
388-396 |
VBG |
denotes |
flanking |
T4676 |
397-400 |
NN |
denotes |
PGK |
T4677 |
401-409 |
NN |
denotes |
neomycin |
T4678 |
400-401 |
HYPH |
denotes |
- |
T4679 |
420-428 |
NN |
denotes |
cassette |
T4680 |
410-419 |
NN |
denotes |
selection |
T4681 |
429-431 |
IN |
denotes |
by |
T4682 |
432-446 |
VBG |
denotes |
recombineering |
T4683 |
447-448 |
-LRB- |
denotes |
[ |
T4684 |
451-453 |
CD |
denotes |
13 |
T4685 |
448-450 |
CD |
denotes |
12 |
T4686 |
450-451 |
, |
denotes |
, |
T4687 |
453-454 |
-RRB- |
denotes |
] |
T4688 |
455-456 |
-LRB- |
denotes |
( |
T4689 |
483-484 |
NN |
denotes |
N |
T4690 |
456-462 |
NN |
denotes |
Figure |
T4691 |
463-465 |
NN |
denotes |
1A |
T4692 |
465-467 |
, |
denotes |
, |
T4693 |
467-474 |
NN |
denotes |
ApcCKON |
T4694 |
475-481 |
NN |
denotes |
allele |
T4695 |
481-483 |
, |
denotes |
, |
T4696 |
485-488 |
IN |
denotes |
for |
T4697 |
489-497 |
NN |
denotes |
neomycin |
T4698 |
498-506 |
NN |
denotes |
cassette |
T4699 |
506-507 |
-RRB- |
denotes |
) |
T4700 |
507-508 |
. |
denotes |
. |
T4701 |
508-629 |
sentence |
denotes |
A PGK-neomycin cassette was inserted in the same transcriptional orientation as Apc in intron 14 of the endogenous gene. |
T4702 |
509-510 |
DT |
denotes |
A |
T4703 |
524-532 |
NN |
denotes |
cassette |
T4704 |
511-514 |
NN |
denotes |
PGK |
T4705 |
515-523 |
NN |
denotes |
neomycin |
T4706 |
514-515 |
HYPH |
denotes |
- |
T4707 |
537-545 |
VBN |
denotes |
inserted |
T4708 |
533-536 |
VBD |
denotes |
was |
T4709 |
546-548 |
IN |
denotes |
in |
T4710 |
549-552 |
DT |
denotes |
the |
T4711 |
574-585 |
NN |
denotes |
orientation |
T4712 |
553-557 |
JJ |
denotes |
same |
T4713 |
558-573 |
JJ |
denotes |
transcriptional |
T4714 |
586-588 |
IN |
denotes |
as |
T4715 |
589-592 |
NN |
denotes |
Apc |
T4716 |
593-595 |
IN |
denotes |
in |
T4717 |
596-602 |
NN |
denotes |
intron |
T4718 |
603-605 |
CD |
denotes |
14 |
T4719 |
606-608 |
IN |
denotes |
of |
T4720 |
609-612 |
DT |
denotes |
the |
T4721 |
624-628 |
NN |
denotes |
gene |
T4722 |
613-623 |
JJ |
denotes |
endogenous |
T4723 |
628-629 |
. |
denotes |
. |
T4724 |
629-707 |
sentence |
denotes |
The loxP and FRT sites were used to aid unidirectional recombination [12,13]. |
T4725 |
630-633 |
DT |
denotes |
The |
T4726 |
647-652 |
NNS |
denotes |
sites |
T4727 |
634-638 |
NN |
denotes |
loxP |
T4728 |
639-642 |
CC |
denotes |
and |
T4729 |
643-646 |
NN |
denotes |
FRT |
T4730 |
658-662 |
VBN |
denotes |
used |
T4731 |
653-657 |
VBD |
denotes |
were |
T4732 |
663-665 |
TO |
denotes |
to |
T4733 |
666-669 |
VB |
denotes |
aid |
T4734 |
670-684 |
JJ |
denotes |
unidirectional |
T4735 |
685-698 |
NN |
denotes |
recombination |
T4736 |
699-700 |
-LRB- |
denotes |
[ |
T4737 |
703-705 |
CD |
denotes |
13 |
T4738 |
700-702 |
CD |
denotes |
12 |
T4739 |
702-703 |
, |
denotes |
, |
T4740 |
705-706 |
-RRB- |
denotes |
] |
T4741 |
706-707 |
. |
denotes |
. |
T4742 |
707-857 |
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 |
708-711 |
CD |
denotes |
Two |
T4744 |
718-723 |
NNS |
denotes |
lines |
T4745 |
712-717 |
NN |
denotes |
mouse |
T4746 |
762-771 |
VBN |
denotes |
generated |
T4747 |
724-734 |
VBG |
denotes |
containing |
T4748 |
735-738 |
DT |
denotes |
the |
T4749 |
744-756 |
NN |
denotes |
modification |
T4750 |
739-743 |
JJ |
denotes |
same |
T4751 |
757-761 |
VBD |
denotes |
were |
T4752 |
772-776 |
IN |
denotes |
from |
T4753 |
777-780 |
CD |
denotes |
two |
T4754 |
796-802 |
NNS |
denotes |
clones |
T4755 |
781-792 |
JJ |
denotes |
independent |
T4756 |
793-795 |
NN |
denotes |
ES |
T4757 |
803-805 |
TO |
denotes |
to |
T4758 |
806-812 |
VB |
denotes |
ensure |
T4759 |
813-817 |
IN |
denotes |
that |
T4760 |
834-840 |
VBP |
denotes |
behave |
T4761 |
818-823 |
DT |
denotes |
these |
T4762 |
828-833 |
NNS |
denotes |
lines |
T4763 |
824-827 |
CD |
denotes |
two |
T4764 |
841-843 |
IN |
denotes |
in |
T4765 |
844-847 |
DT |
denotes |
the |
T4766 |
853-856 |
NN |
denotes |
way |
T4767 |
848-852 |
JJ |
denotes |
same |
T4768 |
856-857 |
. |
denotes |
. |
T4769 |
857-1109 |
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 |
858-863 |
DT |
denotes |
These |
T4771 |
874-878 |
NNS |
denotes |
mice |
T4772 |
864-871 |
NN |
denotes |
ApcCKON |
T4773 |
871-872 |
HYPH |
denotes |
/ |
T4774 |
872-873 |
SYM |
denotes |
+ |
T4775 |
884-891 |
VBN |
denotes |
crossed |
T4776 |
879-883 |
VBD |
denotes |
were |
T4777 |
892-896 |
IN |
denotes |
with |
T4778 |
897-901 |
NN |
denotes |
FLPe |
T4779 |
902-909 |
NN |
denotes |
deleter |
T4780 |
901-902 |
HYPH |
denotes |
- |
T4781 |
910-912 |
TO |
denotes |
to |
T4782 |
913-921 |
VB |
denotes |
generate |
T4783 |
922-928 |
NN |
denotes |
ApcCKO |
T4784 |
931-935 |
NNS |
denotes |
mice |
T4785 |
928-929 |
HYPH |
denotes |
/ |
T4786 |
929-930 |
SYM |
denotes |
+ |
T4787 |
936-940 |
WDT |
denotes |
that |
T4788 |
941-945 |
VBD |
denotes |
were |
T4789 |
946-958 |
JJ |
denotes |
heterozygous |
T4790 |
959-962 |
IN |
denotes |
for |
T4791 |
963-966 |
DT |
denotes |
the |
T4792 |
998-1004 |
NN |
denotes |
allele |
T4793 |
967-972 |
JJ |
denotes |
final |
T4794 |
973-976 |
NN |
denotes |
Apc |
T4795 |
977-988 |
JJ |
denotes |
conditional |
T4796 |
989-990 |
-LRB- |
denotes |
( |
T4797 |
990-996 |
NN |
denotes |
ApcCKO |
T4798 |
996-997 |
-RRB- |
denotes |
) |
T4799 |
1005-1009 |
WDT |
denotes |
that |
T4800 |
1010-1017 |
VBD |
denotes |
removed |
T4801 |
1018-1021 |
DT |
denotes |
the |
T4802 |
1035-1043 |
NN |
denotes |
cassette |
T4803 |
1022-1025 |
NN |
denotes |
PGK |
T4804 |
1026-1034 |
NN |
denotes |
neomycin |
T4805 |
1025-1026 |
HYPH |
denotes |
- |
T4806 |
1044-1047 |
CC |
denotes |
and |
T4807 |
1048-1056 |
VBZ |
denotes |
contains |
T4808 |
1057-1061 |
RB |
denotes |
only |
T4809 |
1071-1076 |
NNS |
denotes |
sites |
T4810 |
1062-1065 |
DT |
denotes |
the |
T4811 |
1066-1070 |
NN |
denotes |
loxP |
T4812 |
1077-1079 |
IN |
denotes |
in |
T4813 |
1080-1083 |
DT |
denotes |
the |
T4814 |
1084-1091 |
NNS |
denotes |
introns |
T4815 |
1092-1100 |
VBG |
denotes |
flanking |
T4816 |
1101-1105 |
NN |
denotes |
exon |
T4817 |
1106-1108 |
CD |
denotes |
14 |
T4818 |
1108-1109 |
. |
denotes |
. |
T4819 |
1109-1290 |
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 |
1110-1112 |
TO |
denotes |
To |
T4821 |
1113-1119 |
VB |
denotes |
assess |
T4822 |
1193-1200 |
VBN |
denotes |
crossed |
T4823 |
1120-1123 |
DT |
denotes |
the |
T4824 |
1124-1130 |
NN |
denotes |
effect |
T4825 |
1131-1133 |
IN |
denotes |
of |
T4826 |
1134-1142 |
VBG |
denotes |
deleting |
T4827 |
1143-1147 |
NN |
denotes |
exon |
T4828 |
1148-1150 |
CD |
denotes |
14 |
T4829 |
1151-1153 |
IN |
denotes |
in |
T4830 |
1154-1158 |
NNS |
denotes |
mice |
T4831 |
1158-1160 |
, |
denotes |
, |
T4832 |
1160-1164 |
DT |
denotes |
both |
T4833 |
1165-1170 |
NNS |
denotes |
lines |
T4834 |
1171-1173 |
IN |
denotes |
of |
T4835 |
1174-1180 |
NN |
denotes |
ApcCKO |
T4836 |
1183-1187 |
NNS |
denotes |
mice |
T4837 |
1180-1181 |
HYPH |
denotes |
/ |
T4838 |
1181-1182 |
SYM |
denotes |
+ |
T4839 |
1188-1192 |
VBD |
denotes |
were |
T4840 |
1201-1205 |
IN |
denotes |
with |
T4841 |
1206-1209 |
DT |
denotes |
the |
T4842 |
1214-1221 |
NN |
denotes |
deleter |
T4843 |
1210-1213 |
NN |
denotes |
Cre |
T4844 |
1213-1214 |
HYPH |
denotes |
- |
T4845 |
1222-1224 |
TO |
denotes |
to |
T4846 |
1225-1233 |
VB |
denotes |
generate |
T4847 |
1234-1237 |
DT |
denotes |
the |
T4848 |
1256-1260 |
NN |
denotes |
line |
T4849 |
1238-1246 |
NN |
denotes |
germline |
T4850 |
1247-1255 |
NN |
denotes |
knockout |
T4851 |
1261-1263 |
IN |
denotes |
of |
T4852 |
1264-1267 |
NNP |
denotes |
Apc |
T4853 |
1267-1269 |
, |
denotes |
, |
T4854 |
1269-1279 |
VBN |
denotes |
designated |
T4855 |
1280-1287 |
NN |
denotes |
ApcΔ580 |
T4856 |
1287-1288 |
HYPH |
denotes |
/ |
T4857 |
1288-1289 |
SYM |
denotes |
+ |
T4858 |
1289-1290 |
. |
denotes |
. |
T4859 |
1290-1345 |
sentence |
denotes |
The mutant allele (ApcΔ580) lacks exon 14 (Figure 1A). |
T4860 |
1291-1294 |
DT |
denotes |
The |
T4861 |
1302-1308 |
NN |
denotes |
allele |
T4862 |
1295-1301 |
JJ |
denotes |
mutant |
T4863 |
1319-1324 |
VBZ |
denotes |
lacks |
T4864 |
1309-1310 |
-LRB- |
denotes |
( |
T4865 |
1310-1317 |
NN |
denotes |
ApcΔ580 |
T4866 |
1317-1318 |
-RRB- |
denotes |
) |
T4867 |
1325-1329 |
NN |
denotes |
exon |
T4868 |
1330-1332 |
CD |
denotes |
14 |
T4869 |
1333-1334 |
-LRB- |
denotes |
( |
T4870 |
1341-1343 |
NN |
denotes |
1A |
T4871 |
1334-1340 |
NN |
denotes |
Figure |
T4872 |
1343-1344 |
-RRB- |
denotes |
) |
T4873 |
1344-1345 |
. |
denotes |
. |
T4874 |
1345-1628 |
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 |
1346-1349 |
DT |
denotes |
The |
T4876 |
1350-1360 |
NN |
denotes |
transcript |
T4877 |
1382-1389 |
VBZ |
denotes |
results |
T4878 |
1361-1365 |
IN |
denotes |
from |
T4879 |
1366-1370 |
NN |
denotes |
loss |
T4880 |
1371-1373 |
IN |
denotes |
of |
T4881 |
1374-1378 |
NN |
denotes |
exon |
T4882 |
1379-1381 |
CD |
denotes |
14 |
T4883 |
1390-1392 |
IN |
denotes |
in |
T4884 |
1393-1394 |
DT |
denotes |
a |
T4885 |
1395-1400 |
NN |
denotes |
shift |
T4886 |
1401-1403 |
IN |
denotes |
in |
T4887 |
1404-1407 |
DT |
denotes |
the |
T4888 |
1423-1428 |
NN |
denotes |
frame |
T4889 |
1408-1414 |
JJ |
denotes |
normal |
T4890 |
1415-1422 |
NN |
denotes |
reading |
T4891 |
1428-1430 |
, |
denotes |
, |
T4892 |
1430-1439 |
VBG |
denotes |
resulting |
T4893 |
1440-1442 |
IN |
denotes |
in |
T4894 |
1443-1444 |
DT |
denotes |
a |
T4895 |
1473-1478 |
NN |
denotes |
codon |
T4896 |
1445-1454 |
JJ |
denotes |
premature |
T4897 |
1455-1460 |
NN |
denotes |
chain |
T4898 |
1461-1472 |
NN |
denotes |
termination |
T4899 |
1479-1484 |
WDT |
denotes |
which |
T4900 |
1505-1511 |
VB |
denotes |
result |
T4901 |
1484-1486 |
, |
denotes |
, |
T4902 |
1486-1488 |
IN |
denotes |
if |
T4903 |
1489-1497 |
VBN |
denotes |
utilized |
T4904 |
1497-1499 |
, |
denotes |
, |
T4905 |
1499-1504 |
MD |
denotes |
would |
T4906 |
1512-1514 |
IN |
denotes |
in |
T4907 |
1515-1516 |
DT |
denotes |
a |
T4908 |
1527-1538 |
NN |
denotes |
polypeptide |
T4909 |
1517-1526 |
VBN |
denotes |
truncated |
T4910 |
1539-1543 |
WDT |
denotes |
that |
T4911 |
1544-1546 |
VBZ |
denotes |
is |
T4912 |
1547-1550 |
CD |
denotes |
605 |
T4913 |
1551-1553 |
NNS |
denotes |
aa |
T4914 |
1554-1556 |
IN |
denotes |
in |
T4915 |
1557-1563 |
NN |
denotes |
length |
T4916 |
1563-1565 |
, |
denotes |
, |
T4917 |
1565-1567 |
IN |
denotes |
of |
T4918 |
1591-1601 |
VBP |
denotes |
correspond |
T4919 |
1568-1573 |
WDT |
denotes |
which |
T4920 |
1574-1577 |
DT |
denotes |
the |
T4921 |
1588-1590 |
NNS |
denotes |
aa |
T4922 |
1578-1583 |
JJ |
denotes |
first |
T4923 |
1584-1587 |
CD |
denotes |
580 |
T4924 |
1602-1604 |
IN |
denotes |
to |
T4925 |
1605-1608 |
DT |
denotes |
the |
T4926 |
1620-1627 |
NN |
denotes |
protein |
T4927 |
1609-1615 |
JJ |
denotes |
normal |
T4928 |
1616-1619 |
NN |
denotes |
Apc |
T4929 |
1627-1628 |
. |
denotes |
. |
T4930 |
1628-3352 |
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 |
3194-3202 |
NNP |
denotes |
Southern |
T4932 |
3203-3207 |
NN |
denotes |
blot |
T4933 |
3208-3216 |
NN |
denotes |
analysis |
T4934 |
3281-3290 |
VBD |
denotes |
confirmed |
T4935 |
3217-3219 |
IN |
denotes |
of |
T4936 |
3220-3224 |
NN |
denotes |
tail |
T4937 |
3225-3228 |
NN |
denotes |
DNA |
T4938 |
3229-3233 |
IN |
denotes |
from |
T4939 |
3234-3236 |
NN |
denotes |
F1 |
T4940 |
3237-3246 |
NN |
denotes |
offspring |
T4941 |
3247-3249 |
IN |
denotes |
of |
T4942 |
3250-3254 |
CC |
denotes |
both |
T4943 |
3255-3262 |
NN |
denotes |
ApcCKON |
T4944 |
3275-3280 |
NNS |
denotes |
lines |
T4945 |
3263-3266 |
CC |
denotes |
and |
T4946 |
3267-3274 |
NN |
denotes |
ApcΔ580 |
T4947 |
3291-3294 |
DT |
denotes |
the |
T4948 |
3304-3316 |
NN |
denotes |
transmission |
T4949 |
3295-3303 |
NN |
denotes |
germline |
T4950 |
3317-3319 |
IN |
denotes |
of |
T4951 |
3320-3328 |
VBN |
denotes |
modified |
T4952 |
3333-3339 |
NN |
denotes |
allele |
T4953 |
3329-3332 |
NN |
denotes |
Apc |
T4954 |
3340-3341 |
-LRB- |
denotes |
( |
T4955 |
3348-3350 |
NN |
denotes |
1B |
T4956 |
3341-3347 |
NN |
denotes |
Figure |
T4957 |
3350-3351 |
-RRB- |
denotes |
) |
T4958 |
3351-3352 |
. |
denotes |
. |
T4959 |
3352-3466 |
sentence |
denotes |
Mice that are heterozygous for ApcΔ580 mutation are viable but have a significantly reduced lifespan (Figure 1C). |
T4960 |
3353-3357 |
NNS |
denotes |
Mice |
T4961 |
3401-3404 |
VBP |
denotes |
are |
T4962 |
3358-3362 |
WDT |
denotes |
that |
T4963 |
3363-3366 |
VBP |
denotes |
are |
T4964 |
3367-3379 |
JJ |
denotes |
heterozygous |
T4965 |
3380-3383 |
IN |
denotes |
for |
T4966 |
3384-3391 |
NN |
denotes |
ApcΔ580 |
T4967 |
3392-3400 |
NN |
denotes |
mutation |
T4968 |
3405-3411 |
JJ |
denotes |
viable |
T4969 |
3412-3415 |
CC |
denotes |
but |
T4970 |
3416-3420 |
VBP |
denotes |
have |
T4971 |
3421-3422 |
DT |
denotes |
a |
T4972 |
3445-3453 |
NN |
denotes |
lifespan |
T4973 |
3423-3436 |
RB |
denotes |
significantly |
T4974 |
3437-3444 |
VBN |
denotes |
reduced |
T4975 |
3454-3455 |
-LRB- |
denotes |
( |
T4976 |
3462-3464 |
NN |
denotes |
1C |
T4977 |
3455-3461 |
NN |
denotes |
Figure |
T4978 |
3464-3465 |
-RRB- |
denotes |
) |
T4979 |
3465-3466 |
. |
denotes |
. |
T4980 |
3466-3591 |
sentence |
denotes |
These results suggested that deletion of exon 14 indeed results in either loss or abnormal function of the Apc gene product. |
T4981 |
3467-3472 |
DT |
denotes |
These |
T4982 |
3473-3480 |
NNS |
denotes |
results |
T4983 |
3481-3490 |
VBD |
denotes |
suggested |
T4984 |
3491-3495 |
IN |
denotes |
that |
T4985 |
3523-3530 |
VBZ |
denotes |
results |
T4986 |
3496-3504 |
NN |
denotes |
deletion |
T4987 |
3505-3507 |
IN |
denotes |
of |
T4988 |
3508-3512 |
NN |
denotes |
exon |
T4989 |
3513-3515 |
CD |
denotes |
14 |
T4990 |
3516-3522 |
RB |
denotes |
indeed |
T4991 |
3531-3533 |
IN |
denotes |
in |
T4992 |
3534-3540 |
CC |
denotes |
either |
T4993 |
3541-3545 |
NN |
denotes |
loss |
T4994 |
3546-3548 |
CC |
denotes |
or |
T4995 |
3549-3557 |
JJ |
denotes |
abnormal |
T4996 |
3558-3566 |
NN |
denotes |
function |
T4997 |
3567-3569 |
IN |
denotes |
of |
T4998 |
3570-3573 |
DT |
denotes |
the |
T4999 |
3583-3590 |
NN |
denotes |
product |
T5000 |
3574-3577 |
NN |
denotes |
Apc |
T5001 |
3578-3582 |
NN |
denotes |
gene |
T5002 |
3590-3591 |
. |
denotes |
. |
T5003 |
3591-3709 |
sentence |
denotes |
ApcΔ580/+ mice have median survival of 5 mo of age (Figure 1C), with progressive signs of rectal bleeding and anemia. |
T5004 |
3592-3599 |
NN |
denotes |
ApcΔ580 |
T5005 |
3602-3606 |
NNS |
denotes |
mice |
T5006 |
3599-3600 |
HYPH |
denotes |
/ |
T5007 |
3600-3601 |
SYM |
denotes |
+ |
T5008 |
3607-3611 |
VBP |
denotes |
have |
T5009 |
3612-3618 |
JJ |
denotes |
median |
T5010 |
3619-3627 |
NN |
denotes |
survival |
T5011 |
3628-3630 |
IN |
denotes |
of |
T5012 |
3631-3632 |
CD |
denotes |
5 |
T5013 |
3633-3635 |
NNS |
denotes |
mo |
T5014 |
3636-3638 |
IN |
denotes |
of |
T5015 |
3639-3642 |
NN |
denotes |
age |
T5016 |
3643-3644 |
-LRB- |
denotes |
( |
T5017 |
3651-3653 |
NN |
denotes |
1C |
T5018 |
3644-3650 |
NN |
denotes |
Figure |
T5019 |
3653-3654 |
-RRB- |
denotes |
) |
T5020 |
3654-3656 |
, |
denotes |
, |
T5021 |
3656-3660 |
IN |
denotes |
with |
T5022 |
3661-3672 |
JJ |
denotes |
progressive |
T5023 |
3673-3678 |
NNS |
denotes |
signs |
T5024 |
3679-3681 |
IN |
denotes |
of |
T5025 |
3682-3688 |
JJ |
denotes |
rectal |
T5026 |
3689-3697 |
NN |
denotes |
bleeding |
T5027 |
3698-3701 |
CC |
denotes |
and |
T5028 |
3702-3708 |
NN |
denotes |
anemia |
T5029 |
3708-3709 |
. |
denotes |
. |
T5030 |
3709-3924 |
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 |
3710-3717 |
JJ |
denotes |
Similar |
T5032 |
3830-3833 |
VBD |
denotes |
had |
T5033 |
3718-3720 |
IN |
denotes |
to |
T5034 |
3721-3724 |
DT |
denotes |
the |
T5035 |
3725-3732 |
NNS |
denotes |
results |
T5036 |
3733-3741 |
VBN |
denotes |
reported |
T5037 |
3742-3746 |
IN |
denotes |
with |
T5038 |
3747-3749 |
DT |
denotes |
an |
T5039 |
3802-3808 |
NN |
denotes |
strain |
T5040 |
3750-3763 |
RB |
denotes |
independently |
T5041 |
3764-3773 |
VBN |
denotes |
generated |
T5042 |
3774-3781 |
NN |
denotes |
ApcΔ580 |
T5043 |
3784-3795 |
JJ |
denotes |
conditional |
T5044 |
3781-3782 |
HYPH |
denotes |
/ |
T5045 |
3782-3783 |
SYM |
denotes |
+ |
T5046 |
3796-3801 |
NN |
denotes |
mouse |
T5047 |
3809-3810 |
-LRB- |
denotes |
[ |
T5048 |
3810-3812 |
CD |
denotes |
14 |
T5049 |
3812-3813 |
-RRB- |
denotes |
] |
T5050 |
3813-3815 |
, |
denotes |
, |
T5051 |
3815-3822 |
NN |
denotes |
ApcΔ580 |
T5052 |
3825-3829 |
NNS |
denotes |
mice |
T5053 |
3822-3823 |
HYPH |
denotes |
/ |
T5054 |
3823-3824 |
SYM |
denotes |
+ |
T5055 |
3834-3838 |
JJR |
denotes |
more |
T5056 |
3844-3847 |
CD |
denotes |
100 |
T5057 |
3839-3843 |
IN |
denotes |
than |
T5058 |
3878-3884 |
NNS |
denotes |
tumors |
T5059 |
3848-3849 |
-LRB- |
denotes |
( |
T5060 |
3855-3857 |
CD |
denotes |
37 |
T5061 |
3849-3852 |
CD |
denotes |
120 |
T5062 |
3853-3854 |
SYM |
denotes |
± |
T5063 |
3857-3859 |
, |
denotes |
, |
T5064 |
3859-3860 |
NN |
denotes |
n |
T5065 |
3863-3865 |
CD |
denotes |
11 |
T5066 |
3861-3862 |
SYM |
denotes |
= |
T5067 |
3865-3866 |
-RRB- |
denotes |
) |
T5068 |
3867-3877 |
JJ |
denotes |
intestinal |
T5069 |
3885-3887 |
IN |
denotes |
at |
T5070 |
3888-3891 |
DT |
denotes |
the |
T5071 |
3892-3896 |
NN |
denotes |
time |
T5072 |
3897-3899 |
IN |
denotes |
of |
T5073 |
3900-3905 |
PRP$ |
denotes |
their |
T5074 |
3906-3911 |
NN |
denotes |
death |
T5075 |
3912-3913 |
-LRB- |
denotes |
( |
T5076 |
3920-3922 |
NN |
denotes |
S1 |
T5077 |
3913-3919 |
NN |
denotes |
Figure |
T5078 |
3922-3923 |
-RRB- |
denotes |
) |
T5079 |
3923-3924 |
. |
denotes |
. |
T5080 |
3924-4006 |
sentence |
denotes |
Inactivation of wild-type Apc is an important prerequisite for tumor development. |
T5081 |
3925-3937 |
NN |
denotes |
Inactivation |
T5082 |
3955-3957 |
VBZ |
denotes |
is |
T5083 |
3938-3940 |
IN |
denotes |
of |
T5084 |
3941-3945 |
JJ |
denotes |
wild |
T5085 |
3946-3950 |
NN |
denotes |
type |
T5086 |
3945-3946 |
HYPH |
denotes |
- |
T5087 |
3951-3954 |
NN |
denotes |
Apc |
T5088 |
3958-3960 |
DT |
denotes |
an |
T5089 |
3971-3983 |
NN |
denotes |
prerequisite |
T5090 |
3961-3970 |
JJ |
denotes |
important |
T5091 |
3984-3987 |
IN |
denotes |
for |
T5092 |
3988-3993 |
NN |
denotes |
tumor |
T5093 |
3994-4005 |
NN |
denotes |
development |
T5094 |
4005-4006 |
. |
denotes |
. |
T5095 |
4006-4267 |
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 |
4007-4009 |
PRP |
denotes |
We |
T5097 |
4010-4018 |
VBD |
denotes |
analyzed |
T5098 |
4019-4021 |
CD |
denotes |
30 |
T5099 |
4033-4039 |
NNS |
denotes |
tumors |
T5100 |
4022-4032 |
JJ |
denotes |
intestinal |
T5101 |
4040-4044 |
IN |
denotes |
from |
T5102 |
4045-4052 |
JJ |
denotes |
ApcΔ580 |
T5103 |
4055-4059 |
NNS |
denotes |
mice |
T5104 |
4052-4053 |
HYPH |
denotes |
/ |
T5105 |
4053-4054 |
SYM |
denotes |
+ |
T5106 |
4060-4062 |
IN |
denotes |
by |
T5107 |
4063-4065 |
FW |
denotes |
in |
T5108 |
4066-4071 |
FW |
denotes |
vitro |
T5109 |
4072-4085 |
NN |
denotes |
transcription |
T5110 |
4086-4089 |
CC |
denotes |
and |
T5111 |
4090-4101 |
NN |
denotes |
translation |
T5112 |
4102-4107 |
NN |
denotes |
assay |
T5113 |
4107-4109 |
, |
denotes |
, |
T5114 |
4109-4112 |
CC |
denotes |
but |
T5115 |
4113-4117 |
NN |
denotes |
none |
T5116 |
4126-4132 |
VBD |
denotes |
showed |
T5117 |
4118-4120 |
IN |
denotes |
of |
T5118 |
4121-4125 |
PRP |
denotes |
them |
T5119 |
4133-4142 |
VBN |
denotes |
truncated |
T5120 |
4147-4155 |
NNS |
denotes |
products |
T5121 |
4143-4146 |
NN |
denotes |
Apc |
T5122 |
4156-4157 |
-LRB- |
denotes |
( |
T5123 |
4169-4173 |
NNS |
denotes |
data |
T5124 |
4157-4168 |
JJ |
denotes |
unpublished |
T5125 |
4173-4174 |
-RRB- |
denotes |
) |
T5126 |
4174-4176 |
, |
denotes |
, |
T5127 |
4176-4186 |
VBG |
denotes |
indicating |
T5128 |
4187-4191 |
IN |
denotes |
that |
T5129 |
4248-4250 |
VBZ |
denotes |
is |
T5130 |
4192-4195 |
DT |
denotes |
the |
T5131 |
4208-4217 |
NN |
denotes |
mechanism |
T5132 |
4196-4200 |
RBS |
denotes |
most |
T5133 |
4201-4207 |
JJ |
denotes |
likely |
T5134 |
4218-4220 |
IN |
denotes |
of |
T5135 |
4221-4225 |
JJ |
denotes |
wild |
T5136 |
4226-4230 |
NN |
denotes |
type |
T5137 |
4225-4226 |
HYPH |
denotes |
- |
T5138 |
4235-4247 |
NN |
denotes |
inactivation |
T5139 |
4231-4234 |
NN |
denotes |
Apc |
T5140 |
4251-4253 |
IN |
denotes |
by |
T5141 |
4254-4261 |
JJ |
denotes |
allelic |
T5142 |
4262-4266 |
NN |
denotes |
loss |
T5143 |
4266-4267 |
. |
denotes |
. |
T5144 |
4267-4465 |
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 |
4268-4271 |
DT |
denotes |
The |
T5146 |
4279-4285 |
NN |
denotes |
allele |
T5147 |
4272-4278 |
JJ |
denotes |
mutant |
T5148 |
4286-4289 |
VBD |
denotes |
had |
T5149 |
4290-4292 |
TO |
denotes |
to |
T5150 |
4296-4306 |
VBN |
denotes |
maintained |
T5151 |
4293-4295 |
VB |
denotes |
be |
T5152 |
4307-4310 |
CC |
denotes |
and |
T5153 |
4311-4322 |
VBN |
denotes |
transmitted |
T5154 |
4323-4330 |
IN |
denotes |
through |
T5155 |
4331-4335 |
JJ |
denotes |
male |
T5156 |
4336-4340 |
NNS |
denotes |
mice |
T5157 |
4340-4342 |
, |
denotes |
, |
T5158 |
4342-4344 |
IN |
denotes |
as |
T5159 |
4363-4367 |
VBD |
denotes |
were |
T5160 |
4345-4352 |
NN |
denotes |
ApcΔ580 |
T5161 |
4355-4362 |
NNS |
denotes |
females |
T5162 |
4352-4353 |
HYPH |
denotes |
/ |
T5163 |
4353-4354 |
SYM |
denotes |
+ |
T5164 |
4368-4378 |
RB |
denotes |
frequently |
T5165 |
4379-4382 |
RB |
denotes |
not |
T5166 |
4383-4390 |
JJ |
denotes |
healthy |
T5167 |
4391-4397 |
RB |
denotes |
enough |
T5168 |
4398-4400 |
TO |
denotes |
to |
T5169 |
4414-4419 |
VB |
denotes |
nurse |
T5170 |
4401-4413 |
RB |
denotes |
successfully |
T5171 |
4420-4425 |
PRP$ |
denotes |
their |
T5172 |
4430-4434 |
NNS |
denotes |
pups |
T5173 |
4426-4429 |
JJ |
denotes |
own |
T5174 |
4435-4442 |
IN |
denotes |
because |
T5175 |
4443-4445 |
IN |
denotes |
of |
T5176 |
4446-4451 |
PRP$ |
denotes |
their |
T5177 |
4458-4464 |
NN |
denotes |
burden |
T5178 |
4452-4457 |
NN |
denotes |
tumor |
T5179 |
4464-4465 |
. |
denotes |
. |
T5180 |
4465-4531 |
sentence |
denotes |
ApcCKO/+ mice were intercrossed to generate ApcCKO/CKO offspring. |
T5181 |
4466-4472 |
NN |
denotes |
ApcCKO |
T5182 |
4475-4479 |
NNS |
denotes |
mice |
T5183 |
4472-4473 |
HYPH |
denotes |
/ |
T5184 |
4473-4474 |
SYM |
denotes |
+ |
T5185 |
4485-4497 |
VBN |
denotes |
intercrossed |
T5186 |
4480-4484 |
VBD |
denotes |
were |
T5187 |
4498-4500 |
TO |
denotes |
to |
T5188 |
4501-4509 |
VB |
denotes |
generate |
T5189 |
4510-4516 |
NN |
denotes |
ApcCKO |
T5190 |
4517-4520 |
NN |
denotes |
CKO |
T5191 |
4516-4517 |
HYPH |
denotes |
/ |
T5192 |
4521-4530 |
NN |
denotes |
offspring |
T5193 |
4530-4531 |
. |
denotes |
. |
T5194 |
4531-4624 |
sentence |
denotes |
Approximately one-quarter of the offspring (17 of 81) were homozygous for the ApcCKO allele. |
T5195 |
4532-4545 |
RB |
denotes |
Approximately |
T5196 |
4546-4549 |
CD |
denotes |
one |
T5197 |
4586-4590 |
VBD |
denotes |
were |
T5198 |
4549-4550 |
HYPH |
denotes |
- |
T5199 |
4550-4557 |
JJ |
denotes |
quarter |
T5200 |
4558-4560 |
IN |
denotes |
of |
T5201 |
4561-4564 |
DT |
denotes |
the |
T5202 |
4565-4574 |
NN |
denotes |
offspring |
T5203 |
4575-4576 |
-LRB- |
denotes |
( |
T5204 |
4576-4578 |
CD |
denotes |
17 |
T5205 |
4579-4581 |
IN |
denotes |
of |
T5206 |
4582-4584 |
CD |
denotes |
81 |
T5207 |
4584-4585 |
-RRB- |
denotes |
) |
T5208 |
4591-4601 |
JJ |
denotes |
homozygous |
T5209 |
4602-4605 |
IN |
denotes |
for |
T5210 |
4606-4609 |
DT |
denotes |
the |
T5211 |
4617-4623 |
NN |
denotes |
allele |
T5212 |
4610-4616 |
NN |
denotes |
ApcCKO |
T5213 |
4623-4624 |
. |
denotes |
. |
T5214 |
4624-4777 |
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 |
4625-4630 |
DT |
denotes |
These |
T5216 |
4631-4635 |
NNS |
denotes |
mice |
T5217 |
4683-4686 |
VBP |
denotes |
are |
T5218 |
4636-4638 |
RB |
denotes |
as |
T5219 |
4644-4646 |
IN |
denotes |
as |
T5220 |
4639-4643 |
RB |
denotes |
well |
T5221 |
4647-4659 |
JJ |
denotes |
heterozygous |
T5222 |
4660-4664 |
NNS |
denotes |
mice |
T5223 |
4665-4668 |
IN |
denotes |
for |
T5224 |
4669-4675 |
NN |
denotes |
ApcCKO |
T5225 |
4676-4682 |
NN |
denotes |
allele |
T5226 |
4687-4693 |
JJ |
denotes |
normal |
T5227 |
4693-4695 |
, |
denotes |
, |
T5228 |
4695-4702 |
VBG |
denotes |
showing |
T5229 |
4703-4705 |
DT |
denotes |
no |
T5230 |
4706-4717 |
NNS |
denotes |
differences |
T5231 |
4718-4720 |
IN |
denotes |
in |
T5232 |
4721-4726 |
PRP$ |
denotes |
their |
T5233 |
4727-4735 |
NN |
denotes |
survival |
T5234 |
4736-4738 |
IN |
denotes |
to |
T5235 |
4739-4742 |
DT |
denotes |
the |
T5236 |
4753-4764 |
NNS |
denotes |
littermates |
T5237 |
4743-4747 |
JJ |
denotes |
wild |
T5238 |
4748-4752 |
NN |
denotes |
type |
T5239 |
4747-4748 |
HYPH |
denotes |
- |
T5240 |
4765-4766 |
-LRB- |
denotes |
( |
T5241 |
4773-4775 |
NN |
denotes |
1C |
T5242 |
4766-4772 |
NN |
denotes |
Figure |
T5243 |
4775-4776 |
-RRB- |
denotes |
) |
T5244 |
4776-4777 |
. |
denotes |
. |
T5245 |
4777-4910 |
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 |
4778-4780 |
PRP |
denotes |
We |
T5247 |
4781-4787 |
VBD |
denotes |
tested |
T5248 |
4788-4795 |
IN |
denotes |
whether |
T5249 |
4818-4828 |
VB |
denotes |
compliment |
T5250 |
4796-4799 |
PRP$ |
denotes |
our |
T5251 |
4807-4813 |
NN |
denotes |
allele |
T5252 |
4800-4806 |
NN |
denotes |
ApcCKO |
T5253 |
4814-4817 |
MD |
denotes |
can |
T5254 |
4829-4832 |
DT |
denotes |
the |
T5255 |
4843-4849 |
NN |
denotes |
allele |
T5256 |
4833-4837 |
JJ |
denotes |
wild |
T5257 |
4838-4842 |
NN |
denotes |
type |
T5258 |
4837-4838 |
HYPH |
denotes |
- |
T5259 |
4850-4852 |
IN |
denotes |
by |
T5260 |
4853-4861 |
VBG |
denotes |
crossing |
T5261 |
4862-4865 |
DT |
denotes |
the |
T5262 |
4877-4883 |
NN |
denotes |
female |
T5263 |
4866-4872 |
NN |
denotes |
ApcCKO |
T5264 |
4873-4876 |
NN |
denotes |
CKO |
T5265 |
4872-4873 |
HYPH |
denotes |
/ |
T5266 |
4884-4888 |
IN |
denotes |
with |
T5267 |
4889-4896 |
NN |
denotes |
ApcΔ580 |
T5268 |
4904-4909 |
NN |
denotes |
mouse |
T5269 |
4896-4897 |
HYPH |
denotes |
/ |
T5270 |
4897-4898 |
SYM |
denotes |
+ |
T5271 |
4899-4903 |
JJ |
denotes |
male |
T5272 |
4909-4910 |
. |
denotes |
. |
T5273 |
4910-5118 |
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 |
4911-4914 |
DT |
denotes |
The |
T5275 |
4937-4946 |
NN |
denotes |
offspring |
T5276 |
4915-4924 |
JJ |
denotes |
resultant |
T5277 |
4925-4931 |
NN |
denotes |
ApcCKO |
T5278 |
4932-4936 |
NN |
denotes |
Δ580 |
T5279 |
4931-4932 |
HYPH |
denotes |
/ |
T5280 |
4947-4951 |
VBD |
denotes |
were |
T5281 |
4952-4958 |
JJ |
denotes |
viable |
T5282 |
4959-4962 |
CC |
denotes |
and |
T5283 |
4963-4967 |
VBN |
denotes |
born |
T5284 |
4968-4970 |
IN |
denotes |
in |
T5285 |
4971-4974 |
DT |
denotes |
the |
T5286 |
4985-4990 |
NN |
denotes |
ratio |
T5287 |
4975-4984 |
JJ |
denotes |
Mendelian |
T5288 |
4990-4992 |
, |
denotes |
, |
T5289 |
4992-5002 |
VBG |
denotes |
suggesting |
T5290 |
5003-5007 |
IN |
denotes |
that |
T5291 |
5063-5067 |
VBP |
denotes |
have |
T5292 |
5008-5011 |
DT |
denotes |
the |
T5293 |
5012-5020 |
NN |
denotes |
presence |
T5294 |
5021-5023 |
IN |
denotes |
of |
T5295 |
5024-5028 |
NN |
denotes |
loxP |
T5296 |
5029-5034 |
NNS |
denotes |
sites |
T5297 |
5035-5037 |
IN |
denotes |
in |
T5298 |
5038-5045 |
NNS |
denotes |
introns |
T5299 |
5046-5054 |
VBG |
denotes |
flanking |
T5300 |
5055-5059 |
NN |
denotes |
exon |
T5301 |
5060-5062 |
CD |
denotes |
14 |
T5302 |
5068-5070 |
DT |
denotes |
no |
T5303 |
5079-5085 |
NN |
denotes |
effect |
T5304 |
5071-5078 |
JJ |
denotes |
adverse |
T5305 |
5086-5088 |
IN |
denotes |
on |
T5306 |
5089-5092 |
DT |
denotes |
the |
T5307 |
5093-5101 |
NN |
denotes |
function |
T5308 |
5102-5104 |
IN |
denotes |
of |
T5309 |
5105-5108 |
DT |
denotes |
the |
T5310 |
5113-5117 |
NN |
denotes |
gene |
T5311 |
5109-5112 |
NN |
denotes |
Apc |
T5312 |
5117-5118 |
. |
denotes |
. |
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 |