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Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase

Nature Genetics volume 11, pages 376–381 (1995)Cite this article

Abstract

The Sod2 gene for Mn–superoxide dismutase (MnSOD), an intramitochondrial free radical scavenging enzyme that is the first line of defense against superoxide produced as a byproduct of oxidative phosphorylation, was inactivated by homologous recombination. Homozygous mutant mice die within the first 10 days of life with a dilated cardiomyopathy, accumulation of lipid in liver and skeletal muscle, and metabolic acidosis. Cytochemical analysis revealed a severe reduction in succinate dehydrogenase (complex II) and aconitase (a TCA cycle enzyme) activities in the heart and, to a lesser extent, in other organs. These findings indicate that MnSOD is required for normal biological function of tissues by maintaining the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide.

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Author notes

  1. Christoph Berger

    Present address: Children's Medical Research Institute, Wentworthville, NSW, 2145, Australia

  2. Yibing Li and Ting-Ting Huang: Y.L. & T.T.H. contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Box 0748, 533 Parnassus, U585L, University of California, San Francisco, California, 94143-0748, USA

    Yibing Li, Linda J. Noble & Pak H. Chan

  2. Department of Pediatrics, University of California, Box 0748, 533 Parnassus, U585L, San Francisco, California, 94143-0748, USA

    Ting-Ting Huang, Elaine J. Carlson, Christoph Berger & Charles J. Epstein

  3. Department of Pathology, University of California, Box 0748, 533 Parnassus, U585L, San Francisco, California, 94143-0748, USA

    Philip C. Ursell, Jean L. Olson & Midori P. Yoshimura

  4. Department of Neurology, University of California, Box 0748, 533 Parnassus, U585L, San Francisco, California, 94143-0748, USA

    Pak H. Chan

  5. Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia, 30322, USA

    Simon Melov & Douglas C. Wallace

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Li, Y., Huang, TT., Carlson, E. et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11, 376–381 (1995). https://doi.org/10.1038/ng1295-376

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