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 pleiotropic phenotype that includes neurodegeneration, immunodeficiency, cancer predisposition and hypersensitivity to ionizing radiation. The gene responsible 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 specific features of the murine Atm- deficient phenotype, including abnormalities in hematopoiesis and radiosensitivity. The data are consistent with the possibility that oxidative stress contributes to some of the clinical features associated with the A-T phenotype.
Peter
Y
Y
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100.
Rotman
G
G
Lotem
J
J
Elson
A
A
Shiloh
Y
Y
Groner
Y
Y
D000818:Animals; D001260:Ataxia Telangiectasia / Q000473:pathology / Q000503:physiopathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002531:Cerebellum / Q000473:pathology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005260:Female; D006130:Growth Disorders / Q000201:enzymology; D006410:Hematopoiesis; D006801:Humans; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases; D011836:Radiation Tolerance; D013154:Spleen / Q000473:pathology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C000606290:SOD1 protein, human; D025521:Tumor Suppressor Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases