Reduction of Purkinje cell pathology in SCA1 transgenic mice by p53 deletion

Mona D. Shahbazian, Harry T. Orr, Huda Y. Zoghbi

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36 Scopus citations


The expansion of a polyglutamine tract in the ataxin-1 protein beyond a critical threshold causes spinocerebellar ataxia type 1 (SCA1). To investigate the mechanism of neuronal degeneration in SCA1, we analyzed the phenotype of an SCA1 transgenic mouse model in the absence of p53, an important regulator of cell death, p53 deficiency did not affect the early features of SCA1 mice such as impaired motor coordination and ataxin-1 nuclear inclusion formation but caused a notable reduction in later pathological features, including Purkinje cell heterotopia, dendritic thinning, and molecular layer shrinkage. To determine if this protective effect was mediated by an anti-apoptotic property of p53 deficiency, we looked for apoptosis in SCA1 mice but failed to detect any evidence of it even in the presence of p53. We propose that p53 acts after the initial pathogenic events in SCA1 to promote the progression of neuronal degeneration in SCA1 mice, but this activity may be unrelated to apoptosis.

Original languageEnglish (US)
Pages (from-to)974-981
Number of pages8
JournalNeurobiology of Disease
Issue number6
StatePublished - 2001

Bibliographical note

Funding Information:
The authors thank Barbara Antalffy for assistance with immunohistochemistry and Dr. Allan Bradley for providing the p53-deficient mice. This work was supported by an NIH predoctoral fellowship to M.D.S. (MH12555-01) and by the Neuropathology core of the Baylor Mental Retardation Research Center (HD24064-14). H.Y.Z. is an investigator with the Howard Hughes Medical Institute.


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