C57BL/6.mCAT mice (MCAT transgenic mice) have a CMV enhancer/chicken beta-actin promoter (CAG; from the pCAGGS vector) driving the expression of a human Catalase (CAT) gene in mitochondria. Hemizygous MCAT mice are viable and fertile. Catalase is an enzyme, normally expressed in peroxisomes, that reduces hydrogen peroxide (H2O2) to water and molecular oxygen, mitigating the potential for H2O2 to cause damage to molecules. Mitochondrial catalase expression in MCAT mice results in a 5.5-month increase in median life span for both males and females. Catalase activity is elevated in heart, skeletal muscle, and brain. Cardiac mitochondria have 50 times higher catalase activity than in wild-type littermates leading to a delay in cardiac pathology. They also display improved cardiac performance with age, reducing their susceptibility to cardiac hypertrophy and failure. The severity of cataracts is reduced at 17 months of age, but rebounds to the level found in wildtype mice by 30 months of age. These MCAT mice also exhibit enhanced exercise performance, reduced age-dependent hearing loss, and reserved insulin sensitivity when fed a high-fat diet. When treated with the antiviral drug azidothymidine (AZT) they have a reduction in cardiomyopathy, and they show a reduction in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced Parkinson's disease. H2O2 production and H2O2-induced aconitase inactivation are attenuated, and the development of mitochondrial deletions is reduced. These mice may be useful for studying the role of reactive oxygen species in mammalian longevity, as well as protection from lung adenocarcinoma.
