Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by a trinucleotide CAG repeat. SCA7 predominantly causes a loss of photoreceptors in the retina and Purkinje cells of the cerebellum. Severe infantile-onset SCA7 also causes renal and cardiac irregularities. Previous reports have shown that SCA7 results in increased susceptibility to DNA damage. Since DNA damage can lead to accumulation of senescent cells, we hypothesized that SCA7 causes an accumulation of senescent cells over the course of disease. A 140-CAG repeat SCA7 mouse model was evaluated for signs of disease-specific involvement in the kidney, heart, and cerebellum, tissues that are commonly affected in the infantile form. We found evidence of significant renal abnormality that coincided with an accumulation of senescent cells in the kidneys of SCA7140Q/5Q mice, based on histology findings in addition to RT-qPCR for the cell cycle inhibitors p16Ink4a and p21Cip1 and senescence-associated ß-galactosidase (SA-ßgal) staining, respectively. The Purkinje layer in the cerebellum of SCA7140Q/5Q mice also displayed SA-ßgal+ cells. These novel findings offer evidence that senescent cells accumulate in affected tissues and may possibly contribute to SCA7’s specific phenotype.
Bibliographical noteFunding Information:
This research was performed with funding support from the Richard M. Schulze Family Foundation (JT, no grant number). https:// www.schulzefamilyfoundation.org/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to acknowledge the work done by Ryan O’Kelly and Luise Angelini from the University of Minnesota Institute on the Biology of Aging and Metabolism (iBAM) and Department of Biochemistry, Molecular Biology and Biophysics for their important contributions of mouse necropsy and tissue acquisition.
© 2022 Miller et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Disease Models, Animal
- Nerve Tissue Proteins/genetics
- Spinocerebellar Ataxias/genetics
- Trinucleotide Repeats
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article