ABSTRACT
In this chapter, the authors trace their research on spinocerebellar ataxia type 1 (SCA1) examining the data for insights into the relative contribution to SCA1 pathogenesis of the CAG repeat tract and its protein context. The protein encoded by the SCA1 gene, ataxin–1, is a novel protein that contains between 792 and 869 amino acids depending on the number of CAG repeats. To gain further insight into progression of disease in the SCA1 transgenic mice, animals have been examined in detail from one mutant SCA1 transgenic mouse line for neurological alterations using several behavioural tests and for morphological changes using routine histology and immunohistochemistry. Targeting of the SCA1 mutation to a single cell type known to be prominently involved in native disease, Purkinje cell, has allowed an evaluation of the relative effects of structural alterations and cellular loss on the development of ataxia in the SCA1 transgenic mice.
