Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA

G. Schilling, H. A. Jinnah, V. Gonzales, M. L. Coonfield, Y. Kim, J. D. Wood, D. L. Price, X. J. Li, N. Jenkins, N. Copeland, T. Moran, C. A. Ross, D. R. Borchelt

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)405-418
Number of pages14
JournalNeurobiology of Disease
Issue number3
StatePublished - 2001

ASJC Scopus subject areas

  • Neurology


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