1. Progressive degeneration in a new Drosophila model of spinocerebellar ataxia type 7.
- Author
-
Sujkowski A, Ranxhi B, Bangash ZR, Chbihi ZM, Prifti MV, Qadri Z, Alam N, Todi SV, and Tsou WL
- Subjects
- Animals, Humans, Drosophila genetics, Animals, Genetically Modified, Disease Progression, Drosophila melanogaster genetics, Retina metabolism, Retina pathology, Drosophila Proteins genetics, Drosophila Proteins metabolism, Spinocerebellar Ataxias genetics, Spinocerebellar Ataxias pathology, Spinocerebellar Ataxias metabolism, Ataxin-7 genetics, Ataxin-7 metabolism, Disease Models, Animal, Peptides metabolism, Peptides genetics
- Abstract
Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder resulting from abnormal expansion of an uninterrupted polyglutamine (polyQ) repeat in its disease protein, ataxin-7 (ATXN7). ATXN7 is part of Spt-Ada-Gcn5 acetyltransferase (SAGA), an evolutionarily conserved transcriptional coactivation complex with critical roles in chromatin remodeling, cell signaling, neurodifferentiation, mitochondrial health and autophagy. SCA7 is dominantly inherited and characterized by genetic anticipation and high repeat-length instability. Patients with SCA7 experience progressive ataxia, atrophy, spasticity, and blindness. There is currently no cure for SCA7, and therapies are aimed at alleviating symptoms to increase quality of life. Here, we report novel Drosophila lines of SCA7 with polyQ repeats in wild-type and human disease patient range. We find that ATXN7 expression has age- and polyQ repeat length-dependent reduction in fruit fly survival and retinal instability, concomitant with increased ATXN7 protein aggregation. These new lines will provide important insight on disease progression that can be used in the future to identify therapeutic targets for SCA7 patients., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF