NR AKMV
AU Schilling,G.; Jinnah,H.A.; Gonzales,V.; Coonfield,M.L.; Kim,Y.; Wood,J.D.; Price,D.L.; Li,X.J.; Jenkins,N.A.; Copeland,N.G.; Moran,T.; Ross,C.A.; Borchelt,D.R.
TI Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA
QU Neurobiology of Disease 2001 Jun; 8(3): 405-18
PT journal article
AB 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.
MH Aggression; Animal; Behavior, Animal/*physiology; Brain/*abnormalities/*physiopathology; Brain Chemistry; Comparative Study; Disease Models, Animal; Dopamine/analysis; Huntington Disease/pathology/*physiopathology; Hyperkinesis/pathology/physiopathology; Male; Mice; Mice, Transgenic; Nerve Tissue Proteins/*genetics; Nuclear Proteins/*genetics; Phenotype; Serotonin/analysis; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
SP englisch
PO USA