Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice

被引:157
作者
Borghesani, PR
Alt, FW [1 ]
Bottaro, A
Davidson, L
Aksoy, S
Rathbun, GA
Roberts, TM
Swat, W
Segal, RA
Gu, YS
机构
[1] Howard Hughes Med Inst, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[3] Dana Farber Canc Inst, Dept Cellular & Mol Biol, Boston, MA 02115 USA
[4] Childrens Hosp, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
关键词
D O I
10.1073/pnas.050584897
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 ail 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.
引用
收藏
页码:3336 / 3341
页数:6
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