Glutathione is essential for early embryogenesis - Analysis of a glutathione synthetase knockout mouse

Andreas Winkler, Runa Njålsson, Katarina Carlsson, Abdelaziz Elgadi, Björn Rozell, Linu Abraham, Nuran Ercal, Zheng Zheng Shi, Michael W. Lieberman, Agne Larsson, Svante Norgren

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Glutathione (GSH) is present in all mammalian tissues and plays a crucial role in many cellular processes. The second and final step in the synthesis involves the formation of GSH from gamma-glutamylcysteine (γ-GC) and glycine and is catalyzed by glutathione synthetase (GS). GS deficiency is a rare autosomal recessive disorder, and is present in patients with a range of phenotypes, from mild hemolytic anemia and metabolic acidosis to severe neurologic disorders or even death in infancy. The substrate for GS, γ-GC, has been suggested as playing a protective role, by substituting for GSH as an antioxidant in GS deficient patients. To examine the role of GS and GSH metabolites in development, we generated mice deficient in GSH by targeted disruption of the GS gene (Gss). Homozygous mice died before embryonic day (E) 7.5, but heterozygous mice survived with no distinct phenotype. GS protein levels and enzyme activity, as well as GSH metabolites, were investigated in multiple tissues. Protein levels and enzyme activity of GS in heterozygous mice were diminished by 50%, while GSH levels remained intact γ-GC could not be detected in any investigated tissue. These data demonstrate that GSH is essential for mammalian development, and GSH synthesis via GS is an indispensable pathway for survival.

Original languageEnglish (US)
Pages (from-to)121-126
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Aug 19 2011


  • γ-Glutamylcysteine
  • Glutathione
  • Glutathione synthetase
  • Glutathione synthetase deficiency
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology


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