Neurobiology of Disease (Jun 2001)
Distinct Behavioral and Neuropathological Abnormalities in Transgenic Mouse Models of HD and DRPLA
- Gabriele Schilling,
- Hyder A. Jinnah,
- Vicky Gonzales,
- Michael L. Coonfield,
- Yujin Kim,
- Jonathan D. Wood,
- Donald L. Price,
- Xiao-Jiang Li,
- Nancy Jenkins,
- Neal Copeland,
- Timothy Moran,
- Christopher A. Ross,
- David R. Borchelt
Affiliations
- Gabriele Schilling
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Hyder A. Jinnah
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Vicky Gonzales
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Michael L. Coonfield
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Yujin Kim
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Jonathan D. Wood
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Donald L. Price
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Xiao-Jiang Li
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Nancy Jenkins
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Neal Copeland
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Timothy Moran
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Christopher A. Ross
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- David R. Borchelt
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; Department of Genetics, Emory University School of Medicine, Atlanta, Georgia, 30322; Mouse Cancer Genetics Program, National Cancer Institute, Frederick Cancer Research & Development Center, Bldg. 539, Room 229, Frederick, Maryland, 21702-1201
- Journal volume & issue
-
Vol. 8,
no. 3
pp. 405 – 418
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.