Characterization of the Antioxidant Status of the Heterozygous Manganese Superoxide Dismutase Knockout Mouse

The antioxidant status of several tissues (liver, kidney, lung, brain, heart, muscle, stomach, and spleen) from heterozygous manganese superoxide dismutase (MnSOD) mutant mice (Sod2−/+) was characterized. The activity of MnSOD was decreased (30 to 80%) in all tissues examined. The levels of mRNA coding for the major antioxidant enzymes (CuZnSOD, catalase, and glutathione peroxidase) were not significantly altered in liver, kidney, heart, lung, or brain in theSod2−/+mice. The activities of the enzymes were not altered in any of these tissues, with the exception of a decrease in glutathione peroxidase activity in muscle in theSod2−/+mice compared to theSod2+/+mice. Thus, there was no up-regulation of the activities of the major antioxidant enzymes to compensate for the decrease in MnSOD activity. Reduced glutathione levels were 30 to 50% lower in the lung, brain, and muscle of theSod2−/+mice compared to the wild-typeSod2+/+mice. In addition, the ratio of GSH/GSSG was decreased approximately 50% inSod2−/+muscle, indicating that the decrease in MnSOD activity in theSod2−/+mice results in some degree of oxidative stress in this tissue.