Abstract
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.
Original language | English (US) |
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Pages (from-to) | 33-42 |
Number of pages | 10 |
Journal | NeuroMolecular Medicine |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - 2002 |
Bibliographical note
Funding 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.
Keywords
- Ataxia
- Disease progression
- Polyglutamine
- SCA1