Catalase transgenic mice: characterization and sensitivity to oxidative stress.

The role of catalase in the antioxidant defense system was studied using transgenic mice [Tg(CAT)] harboring a human genomic clone containing the entire human CAT gene. Catalase activity was 2-fold higher in the tissues of hemizygous [Tg(CAT)(+/o)] mice and 3- to 4-fold higher in the tissues of homozygous [Tg(CAT)(+/+)] mice compared to wild type mice. The human CAT transgene was expressed in a tissue-specific pattern that was similar to the endogenous catalase gene. The levels of other major antioxidant enzymes were not altered in the tissues of the transgenic mice. Hepatocytes and fibroblasts from the Tg(CAT)(+/+) mice were more resistant to hydrogen peroxide-induced cell death but were more sensitive to paraquat and TNFalpha toxicity. Fibroblasts from the Tg(CAT)(+/+) mice showed reduced growth rate in culture without treatment and reduced colony-forming capability after gamma-irradiation compared to fibroblasts from wild type mice. In addition, the Tg(CAT)(+/+) animals were more sensitive to gamma-irradiation.