ATM-DEFICIENT MICE - A PARADIGM OF ATAXIA-TELANGIECTASIA

A murine model of ataxia telangiectasia was created by disrupting the Atm locus via gene targeting. Mice homozygous for the disrupted Atm al lele displayed growth retardation, neurologic dysfunction, male and fe male infertility secondary to the absence of mature gametes, defects i n T lymphocyte maturation, and extreme sensitivity to gamma-irradiatio n. The majority of animals developed malignant thymic lymphomas betwee n 2 and 4 months of age. Several chromosomal anomalies were detected i n one of these tumors. Fibroblasts from these mice grew slowly and exh ibited abnormal radiation-induced G1 checkpoint function. Atm-disrupte d mice recapitulate the ataxia telangiectasia phenotype in humans, pro viding a mammalian model in which to study the pathophysiology of this pleiotropic disorder.