Transgeneic mouse model for the study of spinocerebellar ataxia 17 (SCA17) and polyglutamine (polyQ) related neurodegeneration.
These transgenic mice express human TATA box binding protein,TBP, containing a 71 polyQ repeat expansion, under the control of the mouse prion protein promoter. The 71 polyQ-expansion is detected by Western blot analysis. At 6.5 months of age, hemizygous transgenic mice are smaller than wildtype littermates and appear ungroomed. These transgenic mice have a shortened lifespan of approximately 9 months and begin to die as early as 21 weeks of age. Immunohistochemical and Western blot analysis reveals visible nuclear aggregates of polyQ tracts by 15 weeks of age. Electron microscopic examination of brain tissue shows degeneration of Purkinje cells and axons. Reactive gliosis is observed in the granular and Purkinje layers. Onset of progressive locomotor impairment is 7 weeks of age. Some mice exhibit clasping, spontaneous seizures and tremors.
This mutant mouse strain may be useful in studies of spinocerebellar ataxia 17 (SCA17) and polyglutamine (polyQ) related neurodegeneration.
Publication: Friedman, MJ et al. 2007. Nat Neurosci 10(12):1519-28.