Back to Search
Start Over
Glutathione synthesis is essential for mouse development but not for cell growth in culture.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2000 May 09; Vol. 97 (10), pp. 5101-6. - Publication Year :
- 2000
-
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 gamma-glutamylcysteine synthetase (gammaGCS-HS(tm1)), an essential enzyme in GSH synthesis. Embryos homozygous for gammaGCS-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 proliferation. We also isolated cell lines from homozygous mutant blastocysts in medium containing GSH. These cells also grow indefinitely in GSH-free medium supplemented with N-acetylcysteine and have undetectable levels of GSH; further, they show no changes in mitochondrial morphology as judged by electron microscopy. These data demonstrate that GSH is required for mammalian development but dispensable in cell culture and that the functions of GSH, not GSH itself, are essential for cell growth.
- Subjects :
- Animals
Apoptosis
Blastocyst cytology
Blastocyst drug effects
Cell Division drug effects
Cell Line
Fetal Death
Gastrula physiology
Glutamate-Cysteine Ligase deficiency
Glutamate-Cysteine Ligase genetics
Glutathione deficiency
Glutathione pharmacology
Heterozygote
Homozygote
Mesoderm physiology
Mice
Mice, Knockout
Acetylcysteine pharmacology
Blastocyst physiology
Embryonic and Fetal Development
Glutamate-Cysteine Ligase metabolism
Glutathione biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 97
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 10805773
- Full Text :
- https://doi.org/10.1073/pnas.97.10.5101