TY - JOUR
T1 - Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice
AU - Borghesani, Paul R.
AU - Alt, Frederick W.
AU - Bottaro, Andrea
AU - Davidson, Laurie
AU - Aksoy, Saime
AU - Rathbun, Gary A.
AU - Roberts, Thomas M.
AU - Swat, Wojciech
AU - Segal, Rosalind A.
AU - Gu, Yansong
PY - 2000/3/28
Y1 - 2000/3/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=12944328742&partnerID=8YFLogxK
U2 - 10.1073/pnas.97.7.3336
DO - 10.1073/pnas.97.7.3336
M3 - Article
C2 - 10716718
AN - SCOPUS:12944328742
VL - 97
SP - 3336
EP - 3341
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 7
ER -