Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice

Paul R. Borghesani, Frederick W. Alt, Andrea Bottaro, Laurie Davidson, Saime Aksoy, Gary A. Rathbun, Thomas M. Roberts, Wojciech Swat, Rosalind A. Segal, Yansong Gu

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149 Scopus citations

Abstract

Motor incoordination, immune deficiencies, and an increased risk of cancer are the characteristic features of the hereditary disease ataxia- telangiectasia (A-T), which is caused by mutations in the ATM gene. Through gene targeting, we have generated a line of Atm mutant mice, Atm(y/y) mice. In contrast to other Atm mutant mice, Atm(y/y) mice show a lower incidence of thymic lymphoma and survive beyond a few months of age. Atm(y/y) mice exhibit deficits in motor learning indicative of cerebellar dysfunction. Even though we found no gross cerebellar degeneration in older Atm(y/y) animals, ectopic and abnormally differentiated Purkinje cells were apparent in mutant mice of all ages. These findings establish that some neuropathological abnormalities seen in A-T patients also are present in Atm mutant mice. In addition, we report a previously unrecognized effect of Atm deficiency on development or maintenance of CD4+8+ thymocytes. We discuss these findings in the context of the hypothesis that abnormal development of Purkinje cells and lymphocytes contributes to the pathogenesis of A-T.

Original languageEnglish
Pages (from-to)3336-3341
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number7
DOIs
StatePublished - Mar 28 2000
Externally publishedYes

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    Borghesani, P. R., Alt, F. W., Bottaro, A., Davidson, L., Aksoy, S., Rathbun, G. A., Roberts, T. M., Swat, W., Segal, R. A., & Gu, Y. (2000). Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proceedings of the National Academy of Sciences of the United States of America, 97(7), 3336-3341. https://doi.org/10.1073/pnas.97.7.3336