PMC:539297 / 590-1416
Annnotations
craft-ca-core-dev
{"project":"craft-ca-core-dev","denotations":[{"id":"T75","span":{"begin":61,"end":75},"obj":"CL:0000540"},{"id":"T76","span":{"begin":97,"end":102},"obj":"NCBITaxon:10088"},{"id":"T77","span":{"begin":103,"end":112},"obj":"UBERON:0002037"},{"id":"T78","span":{"begin":153,"end":155},"obj":"UBERON:0002037"},{"id":"T79","span":{"begin":155,"end":159},"obj":"PR:000005591"},{"id":"T80","span":{"begin":200,"end":208},"obj":"CL:0000540"},{"id":"T81","span":{"begin":264,"end":269},"obj":"PR:000010124"},{"id":"T82","span":{"begin":274,"end":278},"obj":"PR:000006252"},{"id":"T83","span":{"begin":289,"end":295},"obj":"CL:0000540"},{"id":"T84","span":{"begin":319,"end":321},"obj":"UBERON:0002037"},{"id":"T85","span":{"begin":321,"end":325},"obj":"PR:000005591"},{"id":"T86","span":{"begin":348,"end":355},"obj":"GO:0010467"},{"id":"T87","span":{"begin":377,"end":385},"obj":"PR:000005591"},{"id":"T88","span":{"begin":427,"end":443},"obj":"PR:000022190"},{"id":"T89","span":{"begin":509,"end":520},"obj":"PR:000006025"},{"id":"T90","span":{"begin":615,"end":624},"obj":"GO:0005764"},{"id":"T91","span":{"begin":664,"end":675},"obj":"GO:0006897"},{"id":"T92","span":{"begin":701,"end":713},"obj":"GO:0005739"},{"id":"T93","span":{"begin":798,"end":807},"obj":"MOP:0000568"}],"text":"To elucidate the consequences of the common JNCL mutation in neuronal cells, we used P4 knock-in mouse cerebella to establish conditionally immortalized CbCln3 wild-type, heterozygous, and homozygous neuronal precursor cell lines, which can be differentiated into MAP-2 and NeuN-positive, neuron-like cells. Homozygous CbCln3Δex7/8 precursor cells express low levels of mutant battenin and, when aged at confluency, accumulate ATPase subunit c. Recessive phenotypes are also observed at sub-confluent growth; cathepsin D transport and processing are altered, although enzyme activity is not significantly affected, lysosomal size and distribution are altered, and endocytosis is reduced. In addition, mitochondria are abnormally elongated, cellular ATP levels are decreased, and survival following oxidative stress is reduced."}
craft-sa-dev
{"project":"craft-sa-dev","denotations":[{"id":"T274","span":{"begin":0,"end":2},"obj":"TO"},{"id":"T275","span":{"begin":3,"end":12},"obj":"VB"},{"id":"T276","span":{"begin":80,"end":84},"obj":"VBD"},{"id":"T277","span":{"begin":13,"end":16},"obj":"DT"},{"id":"T278","span":{"begin":17,"end":29},"obj":"NNS"},{"id":"T279","span":{"begin":30,"end":32},"obj":"IN"},{"id":"T280","span":{"begin":33,"end":36},"obj":"DT"},{"id":"T281","span":{"begin":49,"end":57},"obj":"NN"},{"id":"T282","span":{"begin":37,"end":43},"obj":"JJ"},{"id":"T283","span":{"begin":44,"end":48},"obj":"NN"},{"id":"T284","span":{"begin":58,"end":60},"obj":"IN"},{"id":"T285","span":{"begin":61,"end":69},"obj":"JJ"},{"id":"T286","span":{"begin":70,"end":75},"obj":"NNS"},{"id":"T287","span":{"begin":75,"end":77},"obj":","},{"id":"T288","span":{"begin":77,"end":79},"obj":"PRP"},{"id":"T289","span":{"begin":85,"end":87},"obj":"NN"},{"id":"T290","span":{"begin":103,"end":112},"obj":"NNS"},{"id":"T291","span":{"begin":88,"end":93},"obj":"VB"},{"id":"T292","span":{"begin":93,"end":94},"obj":"HYPH"},{"id":"T293","span":{"begin":94,"end":96},"obj":"RP"},{"id":"T294","span":{"begin":97,"end":102},"obj":"NN"},{"id":"T295","span":{"begin":113,"end":115},"obj":"TO"},{"id":"T296","span":{"begin":116,"end":125},"obj":"VB"},{"id":"T297","span":{"begin":126,"end":139},"obj":"RB"},{"id":"T298","span":{"begin":140,"end":152},"obj":"VBN"},{"id":"T299","span":{"begin":224,"end":229},"obj":"NNS"},{"id":"T300","span":{"begin":153,"end":159},"obj":"NN"},{"id":"T301","span":{"begin":160,"end":164},"obj":"JJ"},{"id":"T302","span":{"begin":165,"end":169},"obj":"NN"},{"id":"T303","span":{"begin":164,"end":165},"obj":"HYPH"},{"id":"T304","span":{"begin":169,"end":171},"obj":","},{"id":"T305","span":{"begin":171,"end":183},"obj":"JJ"},{"id":"T306","span":{"begin":183,"end":185},"obj":","},{"id":"T307","span":{"begin":185,"end":188},"obj":"CC"},{"id":"T308","span":{"begin":189,"end":199},"obj":"JJ"},{"id":"T309","span":{"begin":200,"end":208},"obj":"JJ"},{"id":"T310","span":{"begin":209,"end":218},"obj":"NN"},{"id":"T311","span":{"begin":219,"end":223},"obj":"NN"},{"id":"T312","span":{"begin":229,"end":231},"obj":","},{"id":"T313","span":{"begin":231,"end":236},"obj":"WDT"},{"id":"T314","span":{"begin":244,"end":258},"obj":"VBN"},{"id":"T315","span":{"begin":237,"end":240},"obj":"MD"},{"id":"T316","span":{"begin":241,"end":243},"obj":"VB"},{"id":"T317","span":{"begin":259,"end":263},"obj":"IN"},{"id":"T318","span":{"begin":264,"end":267},"obj":"NN"},{"id":"T319","span":{"begin":279,"end":287},"obj":"JJ"},{"id":"T320","span":{"begin":267,"end":268},"obj":"HYPH"},{"id":"T321","span":{"begin":268,"end":269},"obj":"CD"},{"id":"T322","span":{"begin":270,"end":273},"obj":"CC"},{"id":"T323","span":{"begin":274,"end":278},"obj":"NN"},{"id":"T324","span":{"begin":278,"end":279},"obj":"HYPH"},{"id":"T325","span":{"begin":301,"end":306},"obj":"NNS"},{"id":"T326","span":{"begin":287,"end":289},"obj":","},{"id":"T327","span":{"begin":289,"end":295},"obj":"NN"},{"id":"T328","span":{"begin":296,"end":300},"obj":"JJ"},{"id":"T329","span":{"begin":295,"end":296},"obj":"HYPH"},{"id":"T330","span":{"begin":306,"end":307},"obj":"."},{"id":"T331","span":{"begin":307,"end":444},"obj":"sentence"},{"id":"T332","span":{"begin":308,"end":318},"obj":"JJ"},{"id":"T333","span":{"begin":342,"end":347},"obj":"NNS"},{"id":"T334","span":{"begin":319,"end":329},"obj":"NN"},{"id":"T335","span":{"begin":329,"end":330},"obj":"HYPH"},{"id":"T336","span":{"begin":330,"end":331},"obj":"CD"},{"id":"T337","span":{"begin":332,"end":341},"obj":"NN"},{"id":"T338","span":{"begin":348,"end":355},"obj":"VBP"},{"id":"T339","span":{"begin":356,"end":359},"obj":"JJ"},{"id":"T340","span":{"begin":360,"end":366},"obj":"NNS"},{"id":"T341","span":{"begin":367,"end":369},"obj":"IN"},{"id":"T342","span":{"begin":370,"end":376},"obj":"NN"},{"id":"T343","span":{"begin":377,"end":385},"obj":"NN"},{"id":"T344","span":{"begin":386,"end":389},"obj":"CC"},{"id":"T345","span":{"begin":389,"end":391},"obj":","},{"id":"T346","span":{"begin":391,"end":395},"obj":"WRB"},{"id":"T347","span":{"begin":396,"end":400},"obj":"VBN"},{"id":"T348","span":{"begin":416,"end":426},"obj":"VBP"},{"id":"T349","span":{"begin":401,"end":403},"obj":"IN"},{"id":"T350","span":{"begin":404,"end":414},"obj":"NN"},{"id":"T351","span":{"begin":414,"end":416},"obj":","},{"id":"T352","span":{"begin":427,"end":433},"obj":"NN"},{"id":"T353","span":{"begin":442,"end":443},"obj":"NN"},{"id":"T354","span":{"begin":434,"end":441},"obj":"NN"},{"id":"T355","span":{"begin":443,"end":444},"obj":"."},{"id":"T356","span":{"begin":444,"end":687},"obj":"sentence"},{"id":"T357","span":{"begin":445,"end":454},"obj":"JJ"},{"id":"T358","span":{"begin":455,"end":465},"obj":"NNS"},{"id":"T359","span":{"begin":475,"end":483},"obj":"VBN"},{"id":"T360","span":{"begin":466,"end":469},"obj":"VBP"},{"id":"T361","span":{"begin":470,"end":474},"obj":"RB"},{"id":"T362","span":{"begin":484,"end":486},"obj":"IN"},{"id":"T363","span":{"begin":487,"end":500},"obj":"JJ"},{"id":"T364","span":{"begin":501,"end":507},"obj":"NN"},{"id":"T365","span":{"begin":507,"end":508},"obj":":"},{"id":"T366","span":{"begin":509,"end":518},"obj":"NN"},{"id":"T367","span":{"begin":519,"end":520},"obj":"NN"},{"id":"T368","span":{"begin":550,"end":557},"obj":"VBN"},{"id":"T369","span":{"begin":521,"end":530},"obj":"NN"},{"id":"T370","span":{"begin":531,"end":534},"obj":"CC"},{"id":"T371","span":{"begin":535,"end":545},"obj":"NN"},{"id":"T372","span":{"begin":546,"end":549},"obj":"VBP"},{"id":"T373","span":{"begin":557,"end":559},"obj":","},{"id":"T374","span":{"begin":559,"end":567},"obj":"IN"},{"id":"T375","span":{"begin":605,"end":613},"obj":"VBN"},{"id":"T376","span":{"begin":568,"end":574},"obj":"NN"},{"id":"T377","span":{"begin":575,"end":583},"obj":"NN"},{"id":"T378","span":{"begin":584,"end":586},"obj":"VBZ"},{"id":"T379","span":{"begin":587,"end":590},"obj":"RB"},{"id":"T380","span":{"begin":591,"end":604},"obj":"RB"},{"id":"T381","span":{"begin":651,"end":658},"obj":"VBN"},{"id":"T382","span":{"begin":613,"end":615},"obj":","},{"id":"T383","span":{"begin":615,"end":624},"obj":"JJ"},{"id":"T384","span":{"begin":625,"end":629},"obj":"NN"},{"id":"T385","span":{"begin":630,"end":633},"obj":"CC"},{"id":"T386","span":{"begin":634,"end":646},"obj":"NN"},{"id":"T387","span":{"begin":647,"end":650},"obj":"VBP"},{"id":"T388","span":{"begin":658,"end":660},"obj":","},{"id":"T389","span":{"begin":660,"end":663},"obj":"CC"},{"id":"T390","span":{"begin":664,"end":675},"obj":"NN"},{"id":"T391","span":{"begin":679,"end":686},"obj":"VBN"},{"id":"T392","span":{"begin":676,"end":678},"obj":"VBZ"},{"id":"T393","span":{"begin":686,"end":687},"obj":"."},{"id":"T394","span":{"begin":687,"end":826},"obj":"sentence"},{"id":"T395","span":{"begin":688,"end":690},"obj":"IN"},{"id":"T396","span":{"begin":714,"end":717},"obj":"VBP"},{"id":"T397","span":{"begin":691,"end":699},"obj":"NN"},{"id":"T398","span":{"begin":699,"end":701},"obj":","},{"id":"T399","span":{"begin":701,"end":713},"obj":"NNS"},{"id":"T400","span":{"begin":718,"end":728},"obj":"RB"},{"id":"T401","span":{"begin":729,"end":738},"obj":"JJ"},{"id":"T402","span":{"begin":738,"end":740},"obj":","},{"id":"T403","span":{"begin":740,"end":748},"obj":"JJ"},{"id":"T404","span":{"begin":753,"end":759},"obj":"NNS"},{"id":"T405","span":{"begin":749,"end":752},"obj":"NN"},{"id":"T406","span":{"begin":764,"end":773},"obj":"VBN"},{"id":"T407","span":{"begin":760,"end":763},"obj":"VBP"},{"id":"T408","span":{"begin":773,"end":775},"obj":","},{"id":"T409","span":{"begin":775,"end":778},"obj":"CC"},{"id":"T410","span":{"begin":779,"end":787},"obj":"NN"},{"id":"T411","span":{"begin":818,"end":825},"obj":"VBN"},{"id":"T412","span":{"begin":788,"end":797},"obj":"VBG"},{"id":"T413","span":{"begin":798,"end":807},"obj":"JJ"},{"id":"T414","span":{"begin":808,"end":814},"obj":"NN"},{"id":"T415","span":{"begin":815,"end":817},"obj":"VBZ"},{"id":"T416","span":{"begin":825,"end":826},"obj":"."}],"relations":[{"id":"R92","pred":"aux","subj":"T274","obj":"T275"},{"id":"R93","pred":"advcl","subj":"T275","obj":"T276"},{"id":"R94","pred":"det","subj":"T277","obj":"T278"},{"id":"R95","pred":"dobj","subj":"T278","obj":"T275"},{"id":"R96","pred":"prep","subj":"T279","obj":"T278"},{"id":"R97","pred":"det","subj":"T280","obj":"T281"},{"id":"R98","pred":"pobj","subj":"T281","obj":"T279"},{"id":"R99","pred":"amod","subj":"T282","obj":"T281"},{"id":"R100","pred":"compound","subj":"T283","obj":"T281"},{"id":"R101","pred":"prep","subj":"T284","obj":"T278"},{"id":"R102","pred":"amod","subj":"T285","obj":"T286"},{"id":"R103","pred":"pobj","subj":"T286","obj":"T284"},{"id":"R104","pred":"punct","subj":"T287","obj":"T276"},{"id":"R105","pred":"nsubj","subj":"T288","obj":"T276"},{"id":"R106","pred":"nmod","subj":"T289","obj":"T290"},{"id":"R107","pred":"dobj","subj":"T290","obj":"T276"},{"id":"R108","pred":"amod","subj":"T291","obj":"T290"},{"id":"R109","pred":"punct","subj":"T292","obj":"T291"},{"id":"R110","pred":"prt","subj":"T293","obj":"T291"},{"id":"R111","pred":"compound","subj":"T294","obj":"T290"},{"id":"R112","pred":"aux","subj":"T295","obj":"T296"},{"id":"R113","pred":"advcl","subj":"T296","obj":"T276"},{"id":"R114","pred":"advmod","subj":"T297","obj":"T298"},{"id":"R115","pred":"amod","subj":"T298","obj":"T299"},{"id":"R116","pred":"dobj","subj":"T299","obj":"T296"},{"id":"R117","pred":"nmod","subj":"T300","obj":"T299"},{"id":"R118","pred":"amod","subj":"T301","obj":"T302"},{"id":"R119","pred":"nmod","subj":"T302","obj":"T299"},{"id":"R120","pred":"punct","subj":"T303","obj":"T302"},{"id":"R121","pred":"punct","subj":"T304","obj":"T302"},{"id":"R122","pred":"conj","subj":"T305","obj":"T302"},{"id":"R123","pred":"punct","subj":"T306","obj":"T305"},{"id":"R124","pred":"cc","subj":"T307","obj":"T305"},{"id":"R125","pred":"conj","subj":"T308","obj":"T305"},{"id":"R126","pred":"amod","subj":"T309","obj":"T310"},{"id":"R127","pred":"compound","subj":"T310","obj":"T299"},{"id":"R128","pred":"compound","subj":"T311","obj":"T299"},{"id":"R129","pred":"punct","subj":"T312","obj":"T299"},{"id":"R130","pred":"dep","subj":"T313","obj":"T314"},{"id":"R131","pred":"relcl","subj":"T314","obj":"T299"},{"id":"R132","pred":"aux","subj":"T315","obj":"T314"},{"id":"R133","pred":"auxpass","subj":"T316","obj":"T314"},{"id":"R134","pred":"prep","subj":"T317","obj":"T314"},{"id":"R135","pred":"npadvmod","subj":"T318","obj":"T319"},{"id":"R136","pred":"amod","subj":"T319","obj":"T325"},{"id":"R137","pred":"punct","subj":"T320","obj":"T318"},{"id":"R138","pred":"nummod","subj":"T321","obj":"T318"},{"id":"R139","pred":"cc","subj":"T322","obj":"T318"},{"id":"R140","pred":"conj","subj":"T323","obj":"T318"},{"id":"R141","pred":"punct","subj":"T324","obj":"T319"},{"id":"R142","pred":"pobj","subj":"T325","obj":"T317"},{"id":"R143","pred":"punct","subj":"T326","obj":"T325"},{"id":"R144","pred":"npadvmod","subj":"T327","obj":"T328"},{"id":"R145","pred":"amod","subj":"T328","obj":"T325"},{"id":"R146","pred":"punct","subj":"T329","obj":"T328"},{"id":"R147","pred":"punct","subj":"T330","obj":"T276"},{"id":"R148","pred":"amod","subj":"T332","obj":"T333"},{"id":"R149","pred":"nsubj","subj":"T333","obj":"T338"},{"id":"R150","pred":"nmod","subj":"T334","obj":"T333"},{"id":"R151","pred":"punct","subj":"T335","obj":"T334"},{"id":"R152","pred":"nummod","subj":"T336","obj":"T334"},{"id":"R153","pred":"compound","subj":"T337","obj":"T333"},{"id":"R154","pred":"amod","subj":"T339","obj":"T340"},{"id":"R155","pred":"dobj","subj":"T340","obj":"T338"},{"id":"R156","pred":"prep","subj":"T341","obj":"T340"},{"id":"R157","pred":"compound","subj":"T342","obj":"T343"},{"id":"R158","pred":"pobj","subj":"T343","obj":"T341"},{"id":"R159","pred":"cc","subj":"T344","obj":"T338"},{"id":"R160","pred":"punct","subj":"T345","obj":"T338"},{"id":"R161","pred":"advmod","subj":"T346","obj":"T347"},{"id":"R162","pred":"advcl","subj":"T347","obj":"T348"},{"id":"R163","pred":"conj","subj":"T348","obj":"T338"},{"id":"R164","pred":"prep","subj":"T349","obj":"T347"},{"id":"R165","pred":"pobj","subj":"T350","obj":"T349"},{"id":"R166","pred":"punct","subj":"T351","obj":"T348"},{"id":"R167","pred":"compound","subj":"T352","obj":"T353"},{"id":"R169","pred":"compound","subj":"T354","obj":"T353"},{"id":"R170","pred":"punct","subj":"T355","obj":"T338"},{"id":"R171","pred":"amod","subj":"T357","obj":"T358"},{"id":"R172","pred":"nsubjpass","subj":"T358","obj":"T359"},{"id":"R173","pred":"auxpass","subj":"T360","obj":"T359"},{"id":"R174","pred":"advmod","subj":"T361","obj":"T359"},{"id":"R175","pred":"prep","subj":"T362","obj":"T359"},{"id":"R176","pred":"amod","subj":"T363","obj":"T364"},{"id":"R177","pred":"pobj","subj":"T364","obj":"T362"},{"id":"R178","pred":"punct","subj":"T365","obj":"T359"},{"id":"R179","pred":"compound","subj":"T366","obj":"T367"},{"id":"R180","pred":"nsubjpass","subj":"T367","obj":"T368"},{"id":"R181","pred":"conj","subj":"T368","obj":"T359"},{"id":"R182","pred":"appos","subj":"T369","obj":"T367"},{"id":"R183","pred":"cc","subj":"T370","obj":"T369"},{"id":"R184","pred":"conj","subj":"T371","obj":"T369"},{"id":"R185","pred":"auxpass","subj":"T372","obj":"T368"},{"id":"R186","pred":"punct","subj":"T373","obj":"T368"},{"id":"R187","pred":"mark","subj":"T374","obj":"T375"},{"id":"R188","pred":"advcl","subj":"T375","obj":"T381"},{"id":"R189","pred":"compound","subj":"T376","obj":"T377"},{"id":"R190","pred":"nsubjpass","subj":"T377","obj":"T375"},{"id":"R191","pred":"auxpass","subj":"T378","obj":"T375"},{"id":"R192","pred":"neg","subj":"T379","obj":"T375"},{"id":"R193","pred":"advmod","subj":"T380","obj":"T375"},{"id":"R194","pred":"conj","subj":"T381","obj":"T368"},{"id":"R195","pred":"punct","subj":"T382","obj":"T381"},{"id":"R196","pred":"amod","subj":"T383","obj":"T384"},{"id":"R197","pred":"nsubjpass","subj":"T384","obj":"T381"},{"id":"R198","pred":"cc","subj":"T385","obj":"T384"},{"id":"R199","pred":"conj","subj":"T386","obj":"T384"},{"id":"R200","pred":"auxpass","subj":"T387","obj":"T381"},{"id":"R201","pred":"punct","subj":"T388","obj":"T381"},{"id":"R202","pred":"cc","subj":"T389","obj":"T381"},{"id":"R203","pred":"nsubjpass","subj":"T390","obj":"T391"},{"id":"R205","pred":"auxpass","subj":"T392","obj":"T391"},{"id":"R206","pred":"punct","subj":"T393","obj":"T391"},{"id":"R207","pred":"prep","subj":"T395","obj":"T396"},{"id":"R208","pred":"pobj","subj":"T397","obj":"T395"},{"id":"R209","pred":"punct","subj":"T398","obj":"T396"},{"id":"R210","pred":"nsubj","subj":"T399","obj":"T396"},{"id":"R211","pred":"advmod","subj":"T400","obj":"T401"},{"id":"R212","pred":"acomp","subj":"T401","obj":"T396"},{"id":"R213","pred":"punct","subj":"T402","obj":"T396"},{"id":"R214","pred":"amod","subj":"T403","obj":"T404"},{"id":"R216","pred":"compound","subj":"T405","obj":"T404"},{"id":"R218","pred":"auxpass","subj":"T407","obj":"T406"},{"id":"R219","pred":"punct","subj":"T408","obj":"T406"},{"id":"R220","pred":"cc","subj":"T409","obj":"T406"},{"id":"R221","pred":"nsubjpass","subj":"T410","obj":"T411"},{"id":"R222","pred":"conj","subj":"T411","obj":"T406"},{"id":"R223","pred":"prep","subj":"T412","obj":"T410"},{"id":"R224","pred":"amod","subj":"T413","obj":"T414"},{"id":"R225","pred":"pobj","subj":"T414","obj":"T412"},{"id":"R226","pred":"auxpass","subj":"T415","obj":"T411"},{"id":"R227","pred":"punct","subj":"T416","obj":"T396"},{"id":"R168","pred":"dobj","subj":"T353","obj":"T348"},{"id":"R204","pred":"conj","subj":"T391","obj":"T381"},{"id":"R215","pred":"nsubjpass","subj":"T404","obj":"T406"},{"id":"R217","pred":"conj","subj":"T406","obj":"T396"}],"text":"To elucidate the consequences of the common JNCL mutation in neuronal cells, we used P4 knock-in mouse cerebella to establish conditionally immortalized CbCln3 wild-type, heterozygous, and homozygous neuronal precursor cell lines, which can be differentiated into MAP-2 and NeuN-positive, neuron-like cells. Homozygous CbCln3Δex7/8 precursor cells express low levels of mutant battenin and, when aged at confluency, accumulate ATPase subunit c. Recessive phenotypes are also observed at sub-confluent growth; cathepsin D transport and processing are altered, although enzyme activity is not significantly affected, lysosomal size and distribution are altered, and endocytosis is reduced. In addition, mitochondria are abnormally elongated, cellular ATP levels are decreased, and survival following oxidative stress is reduced."}
craft-ca-core-ex-dev
{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T126","span":{"begin":49,"end":57},"obj":"SO_EXT:sequence_alteration_entity_or_process"},{"id":"T127","span":{"begin":61,"end":75},"obj":"CL:0000540"},{"id":"T128","span":{"begin":70,"end":75},"obj":"CL_GO_EXT:cell"},{"id":"T129","span":{"begin":97,"end":102},"obj":"NCBITaxon:10088"},{"id":"T130","span":{"begin":103,"end":112},"obj":"UBERON:0002037"},{"id":"T131","span":{"begin":153,"end":155},"obj":"UBERON:0002037"},{"id":"T132","span":{"begin":155,"end":159},"obj":"PR_EXT:000005591"},{"id":"T133","span":{"begin":160,"end":169},"obj":"SO_EXT:wild_type_entity_or_quality"},{"id":"T134","span":{"begin":200,"end":208},"obj":"CL:0000540"},{"id":"T135","span":{"begin":219,"end":223},"obj":"CL_GO_EXT:cell"},{"id":"T136","span":{"begin":244,"end":258},"obj":"GO_PATO_RO_EXT:developmental_differentiation_process_or_quality"},{"id":"T137","span":{"begin":264,"end":269},"obj":"PR_EXT:000010124"},{"id":"T138","span":{"begin":274,"end":278},"obj":"PR_EXT:000006252"},{"id":"T139","span":{"begin":289,"end":295},"obj":"CL:0000540"},{"id":"T140","span":{"begin":301,"end":306},"obj":"CL_GO_EXT:cell"},{"id":"T141","span":{"begin":319,"end":321},"obj":"UBERON:0002037"},{"id":"T142","span":{"begin":321,"end":325},"obj":"PR_EXT:000005591"},{"id":"T143","span":{"begin":342,"end":347},"obj":"CL_GO_EXT:cell"},{"id":"T144","span":{"begin":348,"end":355},"obj":"GO:0010467"},{"id":"T145","span":{"begin":370,"end":376},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T146","span":{"begin":377,"end":385},"obj":"PR_EXT:000005591"},{"id":"T147","span":{"begin":396,"end":400},"obj":"GO_PATO_EXT:aging_or_agedness"},{"id":"T148","span":{"begin":427,"end":433},"obj":"GO_EXT:0016887"},{"id":"T149","span":{"begin":427,"end":443},"obj":"PR_EXT:000022190"},{"id":"T150","span":{"begin":501,"end":507},"obj":"GO_EXT:biological_growth_entity_or_process"},{"id":"T151","span":{"begin":509,"end":520},"obj":"PR_EXT:000006025"},{"id":"T152","span":{"begin":521,"end":530},"obj":"GO_EXT:biological_routing_or_transport"},{"id":"T153","span":{"begin":535,"end":545},"obj":"SO_EXT:sequence_alteration_process"},{"id":"T154","span":{"begin":568,"end":574},"obj":"CHEBI_GO_SO_EXT:enzyme"},{"id":"T155","span":{"begin":615,"end":624},"obj":"GO:0005764"},{"id":"T156","span":{"begin":664,"end":675},"obj":"GO:0006897"},{"id":"T157","span":{"begin":701,"end":713},"obj":"GO:0005739"},{"id":"T158","span":{"begin":740,"end":748},"obj":"CL_GO_EXT:cell"},{"id":"T159","span":{"begin":749,"end":752},"obj":"CHEBI_EXT:ATP"},{"id":"T160","span":{"begin":798,"end":807},"obj":"MOP:0000568"}],"text":"To elucidate the consequences of the common JNCL mutation in neuronal cells, we used P4 knock-in mouse cerebella to establish conditionally immortalized CbCln3 wild-type, heterozygous, and homozygous neuronal precursor cell lines, which can be differentiated into MAP-2 and NeuN-positive, neuron-like cells. Homozygous CbCln3Δex7/8 precursor cells express low levels of mutant battenin and, when aged at confluency, accumulate ATPase subunit c. Recessive phenotypes are also observed at sub-confluent growth; cathepsin D transport and processing are altered, although enzyme activity is not significantly affected, lysosomal size and distribution are altered, and endocytosis is reduced. In addition, mitochondria are abnormally elongated, cellular ATP levels are decreased, and survival following oxidative stress is reduced."}