2000
DOI: 10.1073/pnas.97.10.5101
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Glutathione synthesis is essential for mouse development but not for cell growth in culture

Abstract: Glutathione (GSH) is a major source of reducing equivalents in mammalian cells. To examine the role of GSH synthesis in development and cell growth, we generated mice deficient in GSH by a targeted disruption of the heavy subunit of ␥-glutamylcysteine synthetase (␥GCS-HS tm1 ), an essential enzyme in GSH synthesis. Embryos homozygous for ␥GCS-HS tm1 fail to gastrulate, do not form mesoderm, develop distal apoptosis, and die before day 8.5. Lethality results from apoptotic cell death rather than reduced cell pr… Show more

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Cited by 256 publications
(201 citation statements)
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“…Mice bearing mutations of genes that are involved in regulating cellular redox status also show early lethality. For example, mice with mutations in genes such as thioredoxin, selenocysteine tRNA, Ref1, and the Gclc result in developmental failure at implantation (41)(42)(43)(44)(45). Thioredoxin is a selenoprotein that regulates expression of various genes through the redox factor 1 protein (Ref1).…”
Section: Discussionmentioning
confidence: 99%
“…Mice bearing mutations of genes that are involved in regulating cellular redox status also show early lethality. For example, mice with mutations in genes such as thioredoxin, selenocysteine tRNA, Ref1, and the Gclc result in developmental failure at implantation (41)(42)(43)(44)(45). Thioredoxin is a selenoprotein that regulates expression of various genes through the redox factor 1 protein (Ref1).…”
Section: Discussionmentioning
confidence: 99%
“…Alterations in the cellular redox status have been shown to control embryo development in several systems (Earnshaw and Johnson 1987;Gardiner et al 1998;Shi et al 2000;Stasolla et al 2004a;Belmonte et al 2006). In recent studies on B. napus, Belmonte et al (2006) show that the endogenous glutathione redox status [deWned as the ratio of the concentration of the reduced form (GSH) to the concentration of the oxidized plus reduced forms (GSSG + GSH)] can be easily manipulated in culture through applications of buthionine sulfoximine (BSO).…”
Section: Introductionmentioning
confidence: 99%
“…Null mutations in GSH1 result in GSH auxotrophy (14 -16), demonstrating that GSH is essential in yeast. In mammals, GSH is also essential, as demonstrated by the embryonic lethality resulting from disruption of ␥-glutamyl cysteine synthetase and by the inability of blastocysts isolated from such knock-out strains to grow, except in the presence of GSH or the GSH substitute N-acetyl cysteine (17). The reason for the essential requirement of GSH in eukaryotes is not known.…”
mentioning
confidence: 99%