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

  title={Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase},
  author={Yibing Li and Ting-Ting Huang and Elaine J. Carlson and Simon Melov and Philip C. Ursell and Jean L. Olson and Linda J. Noble and Midori Yoshimura and Christophe Berger and Pak H. Chan and Douglas C. Wallace and Charles J. Epstein},
  journal={Nature Genetics},
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… 
The Use of Transgenic and Mutant Mice to Study Oxygen Free Radical Metabolism
It is found that MnSOD is required to maintain the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide, and an independently derived MnSod null mouse on a mixed C57BL/6 and 129Sv background with a different phenotype is reported.
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This study demonstrates that lifelong reduction of MnSOD activity has a negative effect on normal heart function and presents a valuable tool to investigate the mechanism of heart pathology reported in patients bearing different polymorphic variants of the MnS OD gene and to develop new therapeutic strategies through manipulation of the antioxidative defence system.
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A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase
Reactive oxygen species (ROS) have been implicated in a wide range of degenerative processes including amyotrophic lateral sclerosis, ischemic heart disease, Alzheimer disease, Parkinson disease and
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The results showed that ADR caused significant decrease in state 3 respiration and respiratory control ratio using both complex I and II substrates in nontransgenic mice and transgenic mice, suggesting that mitochondrial complex I is sensitive to inactivation by superoxide radicals.
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A role of oxygen free radicals in causing abnormality of female reproduction in mammals is suggested for the first time, through a gain-of-function mechanism.
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Patients with complex I (NADH-CoQ oxidoreductase) deficiency show variable hyperinduction of MnSOD that appears to result in production of excess hydroxyl radicals, which are damaging to proteins, lipids and DNA.


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