Spinocerebellar ataxia type 1 (SCA1) belongs to a family of polyglutamine induced neurodegenerative disorders. Transgenic mice that overexpress a mutant allele of the SCA1 gene develop a progressive ataxia and Purkinje cell pathology. In this report, the pathological importance of a segment of ataxin-1 previously shown to be important for protein-protein interactions was examined. While the absence of a 122 amino acid segment from the protein-protein interaction region of ataxin-1 did not effect the initiation of disease, its absence substantially suppressed the progression of disease in SCA1 transgenic mice. Thus, these data suggest that this region of ataxin-1 has a role in disease progression. Furthermore, these results provide evidence that ataxin-1-induced disease initiation and disease progression involve distinct molecular events.
Bibliographical noteFunding Information:
We thank R. Ehlenfeldt and B. Pinch for assistance in the production and maintenance of trans- genic mice, and Dr. M. MacDonald (MGH) for providing the 1F8 anti-polyQ antibody. This work was supported by grants from the NINDS, NIH (NS35255, NS27699, & NS22920). HYZ is an Investigator of the HHMI.
- Disease progression