Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues.
Selenium-dependent cellular glutathione peroxidase (GPX1) knockout [GPX1(-)] mice were derived from 129/SVJ x C57BL/6 hybrid mice by microinjecting C57BL/6 blastocysts with recombinant embryonic stem cells carrying a target mutation in the GPX1 gene. Experiment 1 was conducted to determine the effects of the GPX1 knockout on the susceptibility of mice to dietary vitamin E and Se deficiency and on the expression of the Se-dependent plasma glutathione peroxidase (GPX3) and phospholipid hydroperoxide glutathione peroxidase (GPX4), and the Se-independent glutathione S-transferase (GST). Eleven GPX1(-) and 11 control mice (5 wk old, six males and five females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) or the basal diet supplemented with 0.5 mg Se/kg (as Na2SeO3) for 13 wk. Experiment 2 was conducted to determine the effect of the GPX1 knockout on the total Se concentration in the liver of Se-adequate mice. Six GPX1(-) and four control mice (5 wk old, half males and females) were fed the basal diet supplemented with 0.2 mg Se/kg and 15 mg of all-rac-alpha-tocopheryl acetate/kg for 5 wk. There was no difference in body weight gain or apparent susceptibility to dietary vitamin E and Se deficiency between the GPX1(-) and control mice. Knockout of GPX1 resulted in almost complete abolishment of GPX1 activity in various tissues, but had no effect on the GPX3 or GPX4 mRNA level and activity or the GST activity in several tissues at either level of dietary Se. The liver total Se concentration in the Se-adequate GPX1(-) mice was only 42% of that in the controls (P < 0. 0001). These results indicate that GPX1 is expressed independently of GPX3 or GPX4 and represents approximately 60% of the total hepatic Se in Se-adequate mice.
Cheng
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Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
Ho
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Ross
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Valentine
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Combs
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Lei
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XG
D000818:Animals; D004032:Diet; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency* / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000378:metabolism*; D015430:Weight Gain
D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium