Elevated Cu/Zn-SOD exacerbates radiation sensitivity and hematopoietic abnormalities of Atm-deficient mice

Patients with the genetic disorder ataxia-telangiectasia (A-T) display a pl eiotropic phenotype that includes neurodegeneration, immunodeficiency, canc er predisposition and hypersensitivity to ionizing radiation. The gene resp onsible is ATM and Atm-knockout mice recapitulate most features of A-T. In order to study the involvement of oxidative stress in the A-T phenotype, we examined mice deficient for Atm and overexpressing human Cu/Zn superoxide dismutase (SOD1). We report that elevated levels of SOD1 exacerbate specifi c features of the murine Atm-deficient phenotype, including abnormalities i n hematopoiesis and radiosensitivity. The data are consistent with the poss ibility that oxidative stress contributes to some of the clinical features associated with the A-T phenotype.