Toluwani Adelaja
Research Mentor: Not Available Not Available
Mentor Department: Not Available, Not Available
Author(s): Toluwani Adelaja, Alexandra F. Putka, Hayley S. McLoughlin
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 3
Abstract
Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disease that is caused by a CAG repeat expansion in the ATXN3 gene. It is an autosomal dominant disease involving degeneration of the central and peripheral nervous system, leading to motor incoordination. People diagnosed with SCA3 tend to survive for 10 to 20 years after disease onset and there is currently no FDA approved cure. The contribution of specific cell types to SCA3 pathogenesis remains unknown; therefore, we harnessed a novel conditional mouse model to silence mutant ATXN3 in select cell types. The conditional Knock-in Q300 model expresses a hyper-expanded 300 CAG repeats in the mouse Atxn3 gene, which can be turned off in cells expressing Cre recombinase. Knock-in Q300 mice were crossed with Sox10-Cre constitutive mice to target neural crest-derived cells and Sox10-Cre inducible mice to target myelinating glia. We validated the cell-type and region-specificity of Cre expression in the brain and dorsal root ganglia (DRG) of both models using a tdTomato reporter. Following immunofluorescent staining and confocal imaging, we found widespread expression of Cre in the brain and DRG of Sox10-constitutive mice. The cell types that were targeted included oligodendrocytes, cerebellar Purkinje cells, Schwann cells, and DRG sensory neurons. In contrast, the Sox10-inducible model showed Cre expression restricted to oligodendrocytes in the brain and Schwann cells in the DRG. This validation study provides the foundation for future molecular and behavioral investigations in both models, pushing forward our understanding of the cell types contributing to SCA3.
