Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice.

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.. 
