Cited by 1,023Mitochondrial Function and PathologyRedox biology and oxidative stressGlutathione Transferases and Polymorphisms

Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice

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Lebovitz, R M, Zhang, H, Vogel, H, Cartwright, J, Dionne, L, Lu, N, Huang, S, Matzuk, M M·1996·Proceedings of the National Academy of Sciences

Abstract

Manganese superoxide dismutase (SOD2) converts superoxide to oxygen plus hydrogen peroxide and serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in humans has been associated with several chronic diseases, including ovarian cancer and type I diabetes, and SOD2 overexpression appears to suppress malignancy in cultured cells. We have produced a line of SOD2 knockout mice (SOD2m1BCM/SOD2m1BCM) that survive up to 3 weeks of age and exhibit several novel pathologic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive motor disturbances characterized by weakness, rapid fatigue, and circling behavior. In addition, SOD2m1BCM/SOD2m1BCM mice older than 7 days exhibit extensive mitochondrial injury within degenerating neurons and cardiac myocytes. Approximately 10% of SOD2m1BCM/SOD2m1BCM mice exhibit markedly enlarged and dilated hearts. These observations indicate that SOD2 deficiency causes increased susceptibility to oxidative mitochondrial injury in central nervous system neurons, cardiac myocytes, and other metabolically active tissues after postnatal exposure to ambient oxygen concentrations. Our SOD2-deficient mice differ from a recently described model in which homozygotes die within the first 5 days of life with severe cardiomyopathy and do not exhibit motor disturbances, central nervous system injury, or ultrastructural evidence of mitochondrial injury.

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Crossref · 10.1073/pnas.93.18.9782

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Research works printed but not linked: 1

  1. Weisiger R. A., Fridovich I. Mitochondrial superoxide simutase. Site of synthesis and intramitochondrial localization. J Biol Chem. 1973 Jul 10;248(13):4793–4796. [PubMed] [Google Scholar]

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Authors
Lebovitz, R. M., Zhang, H., Vogel, H., Cartwright, J., Dionne, L., Lu, N., Huang, S., & Matzuk, M. M.
Affiliations
Baylor College of Medicine (US)
Venue
Proceedings of the National Academy of Sciences
Published
1996-09-03
Volume
93
Issue
18
Pages
9782-9787
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2058821788
Cited by
1,023
References
41
Citations by year
2026: 10 · 2025: 13 · 2024: 15 · 2023: 21 · 2022: 21 · 2021: 22 · 2020: 20 · 2019: 24 · 2018: 27 · 2017: 28 · 2016: 35 · 2015: 37 · 2014: 50 · 2013: 39 · 2012: 54
FWCI
8.08
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
manganese superoxide dismutase, Sod2 knockout mice, mitochondrial superoxide, neurodegeneration, basal ganglia neurons, brainstem neurons, motor disturbances, cardiomyopathy, myocardial injury, perinatal death, anemia, oxidative stress
MeSH terms
Animals, Homozygote, Microscopy, Electron, Mitochondria, Mortality, Cardiomyopathies, Myocardium, Nervous System Diseases, RNA, Messenger, Superoxide Dismutase, Restriction Mapping, Mice

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