Characterization of Transgenic Mice That Overexpress Both Copper Zinc Superoxide Dismutase and Catalase

Abstract

Transgenic mice overexpressing both Cu/ZnSOD and catalase [Tg(SOD1/CAT) ^+/o] were used to evaluate the effects of overexpression of both genes against oxidative stress. Characterization of these transgenic mice revealed that catalase or Cu/ZnSOD activities were two- to fourfold higher in the tissues of transgenic mice compared to wild-type mice, and the activities of the other major antioxidant enzymes were not altered in the tissues of the transgenic mice. The murine embryonic fibroblasts (MEFs) from the Tg(SOD1/CAT) ^+/o and MEFs overexpressing Cu/ZnSOD were more resistant to paraquat cytotoxicity, relative to wild-type MEFs. The MEFs from Tg(SOD1/CAT) ^+/o tended to be more resistant (up to 2.25-fold) to paraquat cytotoxicity than MEFs overexpressing either Cu/ZnSOD or catalase alone. MEFs from Tg(CAT) ^+/o and Tg(SOD1/CAT) ^+/o were equally as resistant to hydrogen peroxide cytotoxicity. However, there were no significant differences in whole animal survival against either paraquat or γ-radiation.