PubMed:11494364 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/11494364","sourcedb":"PubMed","sourceid":"11494364","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/11494364","text":"Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene.\nHuntington's disease (HD) is a neurodegenerative disorder characterized by the expansion of CAG repeats in exon 1 of the HD gene. To clarify the instability of expanded CAG repeats in HD patients, an HD model mouse has been generated by gene replacement with human exon 1 of the HD gene with expansion to 77 CAG repeats. Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues. One or two CAG repeat expansion was found in litters from paternal transmission, whereas contraction of CAG repeat in litters was observed through maternal transmission. Elderly mice show greater CAG repeat instability than younger mice, and a unique case was observed of an expanded 97 CAG repeat mouse. Somatic CAG repeat instability is particularly pronounced in the liver, kidney, stomach, and brain but not in the cerebellum of 100-week-old mice. The same results of expanded CAG repeat instability as observed in this HD model mouse were confirmed in the human brain of HD patients. Glial fibrillary acidic protein (GFAP)-positive cells have been found to be increased in the substantia nigra (SN), globus pallidus (GP), and striatum (St) in the brains of 40-week-old affected mice, although without neuronal cell death. The CAG repeat instability and increase in GFAP-positive cells in this mouse model appear to mirror the abnormalities in HD patients. The HD model mouse may therefore have advantages for investigations of molecular mechanisms underlying instability of CAG repeats.","tracks":[{"project":"c_corpus","denotations":[{"id":"T1","span":{"begin":18,"end":24},"obj":"UBERON:0000479"},{"id":"T2","span":{"begin":34,"end":37},"obj":"CVCL_D569"},{"id":"T3","span":{"begin":38,"end":44},"obj":"SO:0001068"},{"id":"T4","span":{"begin":67,"end":72},"obj":"10090"},{"id":"T5","span":{"begin":67,"end":72},"obj":"D051379"},{"id":"T10","span":{"begin":95,"end":115},"obj":"D006816"},{"id":"T11","span":{"begin":95,"end":115},"obj":"D006816"},{"id":"T14","span":{"begin":116,"end":120},"obj":"SO:0000704"},{"id":"T15","span":{"begin":135,"end":142},"obj":"D004194"},{"id":"T16","span":{"begin":135,"end":142},"obj":"D004194"},{"id":"T19","span":{"begin":153,"end":179},"obj":"D019636"},{"id":"T20","span":{"begin":153,"end":179},"obj":"D019636"},{"id":"T21","span":{"begin":214,"end":217},"obj":"CVCL_D569"},{"id":"T23","span":{"begin":229,"end":233},"obj":"SO:0000147"},{"id":"T22","span":{"begin":229,"end":233},"obj":"PR:P33696"},{"id":"T24","span":{"begin":246,"end":250},"obj":"SO:0000704"},{"id":"T25","span":{"begin":291,"end":294},"obj":"CVCL_D569"},{"id":"T26","span":{"begin":331,"end":336},"obj":"10090"},{"id":"T27","span":{"begin":331,"end":336},"obj":"D051379"},{"id":"T28","span":{"begin":359,"end":363},"obj":"SO:0000704"},{"id":"T29","span":{"begin":381,"end":386},"obj":"D006801"},{"id":"T30","span":{"begin":387,"end":391},"obj":"PR:P33696"},{"id":"T31","span":{"begin":387,"end":391},"obj":"SO:0000147"},{"id":"T32","span":{"begin":404,"end":408},"obj":"SO:0000704"},{"id":"T33","span":{"begin":430,"end":433},"obj":"CVCL_D569"},{"id":"T34","span":{"begin":452,"end":460},"obj":"CHEBI:36080"},{"id":"T35","span":{"begin":473,"end":478},"obj":"D006801"},{"id":"T36","span":{"begin":487,"end":491},"obj":"PR:P33696"},{"id":"T37","span":{"begin":487,"end":491},"obj":"SO:0000147"},{"id":"T38","span":{"begin":498,"end":503},"obj":"10090"},{"id":"T39","span":{"begin":498,"end":503},"obj":"D051379"},{"id":"T40","span":{"begin":504,"end":514},"obj":"P42858"},{"id":"T41","span":{"begin":504,"end":514},"obj":"P42859"},{"id":"T42","span":{"begin":504,"end":514},"obj":"P51111"},{"id":"T43","span":{"begin":504,"end":514},"obj":"PR:000008840"},{"id":"T44","span":{"begin":504,"end":514},"obj":"P51112"},{"id":"T45","span":{"begin":545,"end":550},"obj":"UBERON:6110636"},{"id":"T46","span":{"begin":545,"end":550},"obj":"UBERON:0000955"},{"id":"T47","span":{"begin":586,"end":589},"obj":"CVCL_D569"},{"id":"T48","span":{"begin":590,"end":596},"obj":"SO:0001068"},{"id":"T49","span":{"begin":679,"end":682},"obj":"CVCL_D569"},{"id":"T50","span":{"begin":683,"end":689},"obj":"SO:0001068"},{"id":"T51","span":{"begin":753,"end":757},"obj":"PR:000005054"},{"id":"T53","span":{"begin":753,"end":757},"obj":"O89094"},{"id":"T52","span":{"begin":753,"end":757},"obj":"D051379"},{"id":"T54","span":{"begin":753,"end":757},"obj":"10095"},{"id":"T55","span":{"begin":771,"end":774},"obj":"CVCL_D569"},{"id":"T56","span":{"begin":775,"end":781},"obj":"SO:0001068"},{"id":"T57","span":{"begin":807,"end":811},"obj":"PR:000005054"},{"id":"T59","span":{"begin":807,"end":811},"obj":"O89094"},{"id":"T58","span":{"begin":807,"end":811},"obj":"D051379"},{"id":"T60","span":{"begin":807,"end":811},"obj":"10095"},{"id":"T61","span":{"begin":862,"end":865},"obj":"CVCL_D569"},{"id":"T62","span":{"begin":866,"end":872},"obj":"SO:0001068"},{"id":"T63","span":{"begin":873,"end":878},"obj":"10090"},{"id":"T64","span":{"begin":873,"end":878},"obj":"D051379"},{"id":"T65","span":{"begin":888,"end":891},"obj":"CVCL_D569"},{"id":"T66","span":{"begin":892,"end":898},"obj":"SO:0001068"},{"id":"T67","span":{"begin":945,"end":950},"obj":"UBERON:0002107"},{"id":"T68","span":{"begin":952,"end":958},"obj":"UBERON:0002113"},{"id":"T69","span":{"begin":960,"end":967},"obj":"UBERON:0000945"},{"id":"T70","span":{"begin":973,"end":978},"obj":"UBERON:6110636"},{"id":"T71","span":{"begin":973,"end":978},"obj":"UBERON:0000955"},{"id":"T72","span":{"begin":994,"end":1004},"obj":"UBERON:0002037"},{"id":"T73","span":{"begin":1021,"end":1025},"obj":"PR:000005054"},{"id":"T75","span":{"begin":1021,"end":1025},"obj":"O89094"},{"id":"T74","span":{"begin":1021,"end":1025},"obj":"D051379"},{"id":"T76","span":{"begin":1021,"end":1025},"obj":"10095"},{"id":"T77","span":{"begin":1056,"end":1059},"obj":"CVCL_D569"},{"id":"T78","span":{"begin":1060,"end":1066},"obj":"SO:0001068"},{"id":"T79","span":{"begin":1108,"end":1113},"obj":"10090"},{"id":"T80","span":{"begin":1108,"end":1113},"obj":"D051379"},{"id":"T81","span":{"begin":1136,"end":1141},"obj":"D006801"},{"id":"T82","span":{"begin":1142,"end":1147},"obj":"UBERON:6110636"},{"id":"T83","span":{"begin":1142,"end":1147},"obj":"UBERON:0000955"},{"id":"T84","span":{"begin":1164,"end":1195},"obj":"P47819"},{"id":"T86","span":{"begin":1164,"end":1195},"obj":"P14136"},{"id":"T87","span":{"begin":1164,"end":1195},"obj":"PR:000007939"},{"id":"T88","span":{"begin":1164,"end":1195},"obj":"Q28115"},{"id":"T89","span":{"begin":1164,"end":1195},"obj":"Q58EE9"},{"id":"T90","span":{"begin":1164,"end":1195},"obj":"Q5RA72"},{"id":"T92","span":{"begin":1164,"end":1195},"obj":"P03995"},{"id":"T93","span":{"begin":1164,"end":1195},"obj":"P48677"},{"id":"T85","span":{"begin":1164,"end":1195},"obj":"GO:0045101"},{"id":"T94","span":{"begin":1164,"end":1195},"obj":"GO:0045098"},{"id":"T91","span":{"begin":1164,"end":1195},"obj":"D005904"},{"id":"T99","span":{"begin":1188,"end":1195},"obj":"SO:0000104"},{"id":"T100","span":{"begin":1197,"end":1201},"obj":"P47819"},{"id":"T102","span":{"begin":1197,"end":1201},"obj":"P14136"},{"id":"T103","span":{"begin":1197,"end":1201},"obj":"PR:P03995"},{"id":"T104","span":{"begin":1197,"end":1201},"obj":"PR:000007939"},{"id":"T105","span":{"begin":1197,"end":1201},"obj":"PR:P47819"},{"id":"T106","span":{"begin":1197,"end":1201},"obj":"Q28115"},{"id":"T107","span":{"begin":1197,"end":1201},"obj":"Q58EE9"},{"id":"T108","span":{"begin":1197,"end":1201},"obj":"PR:P14136"},{"id":"T109","span":{"begin":1197,"end":1201},"obj":"Q5RA72"},{"id":"T110","span":{"begin":1197,"end":1201},"obj":"P03995"},{"id":"T111","span":{"begin":1197,"end":1201},"obj":"P48677"},{"id":"T112","span":{"begin":1197,"end":1201},"obj":"PR:Q58EE9"},{"id":"T101","span":{"begin":1197,"end":1201},"obj":"GO:0045101"},{"id":"T113","span":{"begin":1257,"end":1273},"obj":"UBERON:0002038"},{"id":"T114","span":{"begin":1280,"end":1295},"obj":"UBERON:0001875"},{"id":"T115","span":{"begin":1306,"end":1314},"obj":"UBERON:0002435"},{"id":"T116","span":{"begin":1306,"end":1314},"obj":"UBERON:0005383"},{"id":"T118","span":{"begin":1358,"end":1362},"obj":"D051379"},{"id":"T120","span":{"begin":1358,"end":1362},"obj":"10095"},{"id":"T117","span":{"begin":1358,"end":1362},"obj":"PR:000005054"},{"id":"T119","span":{"begin":1358,"end":1362},"obj":"O89094"},{"id":"T121","span":{"begin":1381,"end":1400},"obj":"GO:0070997"},{"id":"T123","span":{"begin":1406,"end":1409},"obj":"CVCL_D569"},{"id":"T124","span":{"begin":1410,"end":1416},"obj":"SO:0001068"},{"id":"T125","span":{"begin":1445,"end":1449},"obj":"P47819"},{"id":"T127","span":{"begin":1445,"end":1449},"obj":"P14136"},{"id":"T128","span":{"begin":1445,"end":1449},"obj":"PR:P03995"},{"id":"T129","span":{"begin":1445,"end":1449},"obj":"PR:000007939"},{"id":"T130","span":{"begin":1445,"end":1449},"obj":"PR:P47819"},{"id":"T131","span":{"begin":1445,"end":1449},"obj":"Q28115"},{"id":"T132","span":{"begin":1445,"end":1449},"obj":"Q58EE9"},{"id":"T133","span":{"begin":1445,"end":1449},"obj":"PR:P14136"},{"id":"T134","span":{"begin":1445,"end":1449},"obj":"Q5RA72"},{"id":"T135","span":{"begin":1445,"end":1449},"obj":"P03995"},{"id":"T136","span":{"begin":1445,"end":1449},"obj":"P48677"},{"id":"T137","span":{"begin":1445,"end":1449},"obj":"PR:Q58EE9"},{"id":"T126","span":{"begin":1445,"end":1449},"obj":"GO:0045101"},{"id":"T138","span":{"begin":1473,"end":1478},"obj":"10090"},{"id":"T139","span":{"begin":1473,"end":1478},"obj":"D051379"},{"id":"T140","span":{"begin":1549,"end":1554},"obj":"10090"},{"id":"T141","span":{"begin":1549,"end":1554},"obj":"D051379"},{"id":"T142","span":{"begin":1654,"end":1657},"obj":"CVCL_D569"}],"attributes":[{"subj":"T1","pred":"source","obj":"c_corpus"},{"subj":"T2","pred":"source","obj":"c_corpus"},{"subj":"T3","pred":"source","obj":"c_corpus"},{"subj":"T4","pred":"source","obj":"c_corpus"},{"subj":"T5","pred":"source","obj":"c_corpus"},{"subj":"T10","pred":"source","obj":"c_corpus"},{"subj":"T11","pred":"source","obj":"c_corpus"},{"subj":"T14","pred":"source","obj":"c_corpus"},{"subj":"T15","pred":"source","obj":"c_corpus"},{"subj":"T16","pred":"source","obj":"c_corpus"},{"subj":"T19","pred":"source","obj":"c_corpus"},{"subj":"T20","pred":"source","obj":"c_corpus"},{"subj":"T21","pred":"source","obj":"c_corpus"},{"subj":"T23","pred":"source","obj":"c_corpus"},{"subj":"T22","pred":"source","obj":"c_corpus"},{"subj":"T24","pred":"source","obj":"c_corpus"},{"subj":"T25","pred":"source","obj":"c_corpus"},{"subj":"T26","pred":"source","obj":"c_corpus"},{"subj":"T27","pred":"source","obj":"c_corpus"},{"subj":"T28","pred":"source","obj":"c_corpus"},{"subj":"T29","pred":"source","obj":"c_corpus"},{"subj":"T30","pred":"source","obj":"c_corpus"},{"subj":"T31","pred":"source","obj":"c_corpus"},{"subj":"T32","pred":"source","obj":"c_corpus"},{"subj":"T33","pred":"source","obj":"c_corpus"},{"subj":"T34","pred":"source","obj":"c_corpus"},{"subj":"T35","pred":"source","obj":"c_corpus"},{"subj":"T36","pred":"source","obj":"c_corpus"},{"subj":"T37","pred":"source","obj":"c_corpus"},{"subj":"T38","pred":"source","obj":"c_corpus"},{"subj":"T39","pred":"source","obj":"c_corpus"},{"subj":"T40","pred":"source","obj":"c_corpus"},{"subj":"T41","pred":"source","obj":"c_corpus"},{"subj":"T42","pred":"source","obj":"c_corpus"},{"subj":"T43","pred":"source","obj":"c_corpus"},{"subj":"T44","pred":"source","obj":"c_corpus"},{"subj":"T45","pred":"source","obj":"c_corpus"},{"subj":"T46","pred":"source","obj":"c_corpus"},{"subj":"T47","pred":"source","obj":"c_corpus"},{"subj":"T48","pred":"source","obj":"c_corpus"},{"subj":"T49","pred":"source","obj":"c_corpus"},{"subj":"T50","pred":"source","obj":"c_corpus"},{"subj":"T51","pred":"source","obj":"c_corpus"},{"subj":"T53","pred":"source","obj":"c_corpus"},{"subj":"T52","pred":"source","obj":"c_corpus"},{"subj":"T54","pred":"source","obj":"c_corpus"},{"subj":"T55","pred":"source","obj":"c_corpus"},{"subj":"T56","pred":"source","obj":"c_corpus"},{"subj":"T57","pred":"source","obj":"c_corpus"},{"subj":"T59","pred":"source","obj":"c_corpus"},{"subj":"T58","pred":"source","obj":"c_corpus"},{"subj":"T60","pred":"source","obj":"c_corpus"},{"subj":"T61","pred":"source","obj":"c_corpus"},{"subj":"T62","pred":"source","obj":"c_corpus"},{"subj":"T63","pred":"source","obj":"c_corpus"},{"subj":"T64","pred":"source","obj":"c_corpus"},{"subj":"T65","pred":"source","obj":"c_corpus"},{"subj":"T66","pred":"source","obj":"c_corpus"},{"subj":"T67","pred":"source","obj":"c_corpus"},{"subj":"T68","pred":"source","obj":"c_corpus"},{"subj":"T69","pred":"source","obj":"c_corpus"},{"subj":"T70","pred":"source","obj":"c_corpus"},{"subj":"T71","pred":"source","obj":"c_corpus"},{"subj":"T72","pred":"source","obj":"c_corpus"},{"subj":"T73","pred":"source","obj":"c_corpus"},{"subj":"T75","pred":"source","obj":"c_corpus"},{"subj":"T74","pred":"source","obj":"c_corpus"},{"subj":"T76","pred":"source","obj":"c_corpus"},{"subj":"T77","pred":"source","obj":"c_corpus"},{"subj":"T78","pred":"source","obj":"c_corpus"},{"subj":"T79","pred":"source","obj":"c_corpus"},{"subj":"T80","pred":"source","obj":"c_corpus"},{"subj":"T81","pred":"source","obj":"c_corpus"},{"subj":"T82","pred":"source","obj":"c_corpus"},{"subj":"T83","pred":"source","obj":"c_corpus"},{"subj":"T84","pred":"source","obj":"c_corpus"},{"subj":"T86","pred":"source","obj":"c_corpus"},{"subj":"T87","pred":"source","obj":"c_corpus"},{"subj":"T88","pred":"source","obj":"c_corpus"},{"subj":"T89","pred":"source","obj":"c_corpus"},{"subj":"T90","pred":"source","obj":"c_corpus"},{"subj":"T92","pred":"source","obj":"c_corpus"},{"subj":"T93","pred":"source","obj":"c_corpus"},{"subj":"T85","pred":"source","obj":"c_corpus"},{"subj":"T94","pred":"source","obj":"c_corpus"},{"subj":"T91","pred":"source","obj":"c_corpus"},{"subj":"T99","pred":"source","obj":"c_corpus"},{"subj":"T100","pred":"source","obj":"c_corpus"},{"subj":"T102","pred":"source","obj":"c_corpus"},{"subj":"T103","pred":"source","obj":"c_corpus"},{"subj":"T104","pred":"source","obj":"c_corpus"},{"subj":"T105","pred":"source","obj":"c_corpus"},{"subj":"T106","pred":"source","obj":"c_corpus"},{"subj":"T107","pred":"source","obj":"c_corpus"},{"subj":"T108","pred":"source","obj":"c_corpus"},{"subj":"T109","pred":"source","obj":"c_corpus"},{"subj":"T110","pred":"source","obj":"c_corpus"},{"subj":"T111","pred":"source","obj":"c_corpus"},{"subj":"T112","pred":"source","obj":"c_corpus"},{"subj":"T101","pred":"source","obj":"c_corpus"},{"subj":"T113","pred":"source","obj":"c_corpus"},{"subj":"T114","pred":"source","obj":"c_corpus"},{"subj":"T115","pred":"source","obj":"c_corpus"},{"subj":"T116","pred":"source","obj":"c_corpus"},{"subj":"T118","pred":"source","obj":"c_corpus"},{"subj":"T120","pred":"source","obj":"c_corpus"},{"subj":"T117","pred":"source","obj":"c_corpus"},{"subj":"T119","pred":"source","obj":"c_corpus"},{"subj":"T121","pred":"source","obj":"c_corpus"},{"subj":"T123","pred":"source","obj":"c_corpus"},{"subj":"T124","pred":"source","obj":"c_corpus"},{"subj":"T125","pred":"source","obj":"c_corpus"},{"subj":"T127","pred":"source","obj":"c_corpus"},{"subj":"T128","pred":"source","obj":"c_corpus"},{"subj":"T129","pred":"source","obj":"c_corpus"},{"subj":"T130","pred":"source","obj":"c_corpus"},{"subj":"T131","pred":"source","obj":"c_corpus"},{"subj":"T132","pred":"source","obj":"c_corpus"},{"subj":"T133","pred":"source","obj":"c_corpus"},{"subj":"T134","pred":"source","obj":"c_corpus"},{"subj":"T135","pred":"source","obj":"c_corpus"},{"subj":"T136","pred":"source","obj":"c_corpus"},{"subj":"T137","pred":"source","obj":"c_corpus"},{"subj":"T126","pred":"source","obj":"c_corpus"},{"subj":"T138","pred":"source","obj":"c_corpus"},{"subj":"T139","pred":"source","obj":"c_corpus"},{"subj":"T140","pred":"source","obj":"c_corpus"},{"subj":"T141","pred":"source","obj":"c_corpus"},{"subj":"T142","pred":"source","obj":"c_corpus"}]},{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":121},"obj":"DRI_Outcome"},{"id":"T2","span":{"begin":122,"end":251},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":252,"end":442},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":443,"end":574},"obj":"DRI_Background"},{"id":"T5","span":{"begin":575,"end":744},"obj":"DRI_Outcome"},{"id":"T6","span":{"begin":745,"end":879},"obj":"DRI_Outcome"},{"id":"T7","span":{"begin":880,"end":1026},"obj":"DRI_Challenge"},{"id":"T8","span":{"begin":1027,"end":1163},"obj":"DRI_Outcome"},{"id":"T9","span":{"begin":1164,"end":1401},"obj":"DRI_Background"},{"id":"T10","span":{"begin":1402,"end":1535},"obj":"DRI_Outcome"},{"id":"T11","span":{"begin":1536,"end":1666},"obj":"DRI_Outcome"}],"attributes":[{"subj":"T1","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T2","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T3","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T4","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T5","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T6","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T7","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T8","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T9","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T10","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T11","pred":"source","obj":"UseCases_ArguminSci_Discourse"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"11494364-9#43#47#gene2670","span":{"begin":1445,"end":1449},"obj":"gene2670"},{"id":"11494364-9#121#123#diseaseC0020179","span":{"begin":1523,"end":1525},"obj":"diseaseC0020179"}],"relations":[{"id":"43#47#gene2670121#123#diseaseC0020179","pred":"associated_with","subj":"11494364-9#43#47#gene2670","obj":"11494364-9#121#123#diseaseC0020179"}],"attributes":[{"subj":"11494364-9#43#47#gene2670","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11494364-9#121#123#diseaseC0020179","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"c_corpus","color":"#93a5ec","default":true},{"id":"UseCases_ArguminSci_Discourse","color":"#bfec93"},{"id":"DisGeNET5_gene_disease","color":"#ec93d9"}]}]}}