title: Susceptibility of heterozygous MnSOD gene-knockout mice to oxygen toxicity.
abstract: Recent studies have shown that homozygous Mn superoxide dismutase (Sod2) gene-knockout mice (Sod2(-/-)) die shortly after birth with extensive myocardial injury, whereas heterozygous mutants (Sod2(+/-)) are phenotypically normal in room air. In the current study, we showed that Sod2(+/-) mice with approximately 50% of normal pulmonary MnSOD activity and normal levels of lung CuZnSOD, catalase, and glutathione peroxidase activities were not substantially more susceptible to 100% O2 toxicity than their normal Sod2(+/+) littermates. The mean (+/- SD) survival of Sod2(+/-) mice in 100% O2 was 101.4 +/- 14.8 h (n = 20) versus 103.2 +/- 11.3 h (n = 20) for Sod2(+/+) littermates (P > 0.60). In addition, Sod2(+/-) mice with approximately 50% of normal heart MnSOD activity and Sod2(+/+) mice did not develop any ultrastructural abnormalities in the myocardium at 75 h or 90 h after 100% O2 exposure. These results suggest that in mice, only 50% of MnSOD activity may be sufficient for normal resistance to 100% O2 toxicity.
authors.affiliation: Research and Laboratory Services, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, NY, USA. TSAN.MIN-FU@ALBANY.VA.GOV
authors.forename: M F
authors.initials: MF
authors.lastname: Tsan
authors.forename: J E
authors.initials: JE
authors.lastname: White
authors.forename: B
authors.initials: B
authors.lastname: Caska
authors.forename: C J
authors.initials: CJ
authors.lastname: Epstein
authors.forename: C Y
authors.initials: CY
authors.lastname: Lee
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006579:Heterozygote; D018496:Hyperoxia / Q000201:enzymology* / Q000473:pathology; D008168:Lung / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D010100:Oxygen / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010100:Oxygen