Reduced fertility in female mice lacking copper-zinc superoxide dismutase

被引:264
作者
Ho, YS
Gargano, M
Cao, J
Bronson, RT
Heimler, I
Hutz, RJ
机构
[1] Wayne State Univ, Inst Chem Toxicol, Detroit, MI 48201 USA
[2] Wayne State Univ, Dept Biochem & Mol Biol, Detroit, MI 48201 USA
[3] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA
[4] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA
关键词
D O I
10.1074/jbc.273.13.7765
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Copper-zinc superoxide dismutase (CuZn-SOD) is believed to play a major role in the first line of antioxidant defense by catalyzing the dismutation of superoxide anion radicals to form hydrogen peroxide and molecular oxygen. Recent studies have shown that missense mutations in this gene contribute, evidently through a gain-of-function mechanism, to about 20% of familial amyotrophic lateral sclerosis. To define further the physiologic role of this enzyme, a model of mice deficient in this enzyme was generated using gene targeting technology. Mice lacking this enzyme were apparently healthy and displayed no increased sensitivity to hyperoxia, However, they exhibited a pronounced susceptibility to paraquat toxicity. Most surprisingly, female homozygous knock out mice showed a markedly reduced fertility compared with that of wild-type and heterozygous knock-out mice, Further studies revealed that although these mice ovulated and conceived normally, they exhibited a marked increase in embryonic lethality. These data, for the first time, suggest a role of oxygen free radicals in causing abnormality of female reproduction in mammals.
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页码:7765 / 7769
页数:5
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