Abstract:
:Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA) are autosomal dominant, neurodegenerative disorders caused by the expansion of polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We have previously generated mouse models of these disorders, using transgenes expressed via the prion protein promoter. Here, we report the first direct comparison of abnormalities in these models. The HD mice show abbreviated lifespans (4-6 months), hypoactivity, and mild impairment of motor skills. The DRPLA mice show severe tremors, are hyperactive, and are profoundly uncoordinated. Neuropathological analyses reveal that the distribution of diffuse nuclear immunolabeling and neuronal intranuclear inclusions (NII's), in the CNS of both models, was remarkably similar. Cytoplasmic aggregates of huntingtin were the major distinguishing neuropathological feature of the HD mice; mutant atrophin-1 accumulated/aggregated only in the nucleus. We suggest that the distinct behavioral and neuropathological phenotypes in these mice reflect differences in the way these mutant proteins perturb neuronal function.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Schilling G,Jinnah HA,Gonzales V,Coonfield ML,Kim Y,Wood JD,Price DL,Li XJ,Jenkins N,Copeland N,Moran T,Ross CA,Borchelt DRdoi
10.1006/nbdi.2001.0385keywords:
subject
Has Abstractpub_date
2001-06-01 00:00:00pages
405-18issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(01)90385-7journal_volume
8pub_type
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