title: Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury.
abstract: Catalase plays a major role in cellular antioxidant defense by decomposing hydrogen peroxide, thereby preventing the generation of hydroxyl radical by the Fenton reaction. The degree of catalase deficiency in acatalasemic and hypocatalasemic mice varies from tissue to tissue. They therefore may not be suitable for studying the function of this enzyme in certain models of oxidant-mediated tissue injury. We sought to generate a new line of catalase null mice by the gene targeting technique. The mouse catalase (Cat or Cas1) gene was disrupted by replacing parts of intron 4 and exon 5 with a neomycin resistance cassette. Homozygous Cat knockout mice, which are completely deficient in catalase expression, develop normally and show no gross abnormalities. Slices of liver and lung and lenses from the knockout mice exhibited a retarded rate in decomposing extracellular hydrogen peroxide compared with those of wild-type mice. However, mice deficient in catalase were not more vulnerable to hyperoxia-induced lung injury; nor did their lenses show any increased susceptibility to oxidative stress generated by photochemical reaction, suggesting that the antioxidant function of catalase in these two models of oxidant injury is negligible. Further studies showed that cortical injury from physical impact caused a significant decrease in NAD-linked electron transfer activities and energy coupling capacities in brain mitochondria of Cat knockout mice but not wild-type mice. The observed decrease in efficiency of mitochondrial respiration may be a direct result of an increase in mitochondrion-associated calcium, which is secondary to the increased oxidative stress. These studies suggest that the role of catalase in antioxidant defense is dependent on the type of tissue and the model of oxidant-mediated tissue injury.
authors.affiliation: Institute of Environmental Health Sciences and Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, Michigan 48201, USA. yho@wayne.edu
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.forename: Wanchao
authors.initials: W
authors.lastname: Ma
authors.forename: Abraham
authors.initials: A
authors.lastname: Spector
authors.forename: Dorothy S
authors.initials: DS
authors.lastname: Ho
mesh_terms: D000483:Alleles; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism; D002374:Catalase / Q000235:genetics* / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D004583:Electrons; D005091:Exons; D018390:Gene Targeting; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology*; D017665:Hydroxyl Radical; D000860:Hypoxia / Q000378:metabolism; D007438:Introns; D007908:Lens, Crystalline / Q000378:metabolism; D008027:Light; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D009355:Neomycin / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry* / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010641:Phenotype; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D018076:DNA, Complementary; D016877:Oxidants; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D012313:RNA; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D009355:Neomycin; D010100:Oxygen