Global Gclm KO (Gclm-/-) strain

The Gclm KOstrain was developed and characterized by Yang et al. (1). Gclm KOmice have 10–40% normal GSH levels in tissues (1). Except when challenged with oxidant stress, these mice exhibit no overt phenotype (2). We recently showed Gclm KO mice, despite having increased oxidative stress, are unexpectedly protected against alcohol-induced steatosis and hepatocyte damage (3). These mice represent a model wherein significant GSH depletion in the liver is associated with beneficial metabolic and stress responses to ethanol.

References

  1. Yang Y, Dieter MZ, Chen Y, Shertzer HG, Nebert DW, Dalton TP. (2002). Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(-/-) knockout mouse. Novel model system for a severely compromised oxidative stress response. J Biol Chem 277: 49446-52.
  2. Chen Y, Dong H, Thompson DC, Shertzer HG, Nebert DW, Vasiliou V. (2013). Glutathione defense mechanism in liver injury: insights from animal models. Food Chem Toxicol 60: 38-44.
  3. Chen Y, Singh S, Matsumoto A, Manna SK, Abdelmegeed MA, Golla S, Murphy RC, Dong H, Song BJ, Gonzalez FJ, Thompson DC, Vasiliou V. (2016). Chronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway. Sci Rep 6: 29743.