Conditional Gclcf/f floxed strain

Germ-line deletion of the Gclc gene is embryonic lethal (1). The Gclc floxed conditional KO (Gclcf/f) strain was developed by Chen et al. (2). Expression of GCLC and GCLM proteins and tissue GSH levels are comparable between wild-type and Gclcf/f mice. When crossed with a CRE recombinase-expressing mouse line, mouse lines harboring the Gclc deletion in a time- and/or cell-specific manner can be generated. Through this process, we have developed a hepatocyte-specific Gclch/h KO strain (2) and others have developed (or are developing) unique mouse models with GSH deficiency in specific cell subpopulations. For example, Mak et al. generated a Gclc T cell-specific knockout (3) and we have generated a Gclc surface ectoderm knockout mice that exhibits a severe microphthalmia phenotype (manuscript in preparation).

References

  1. Chen Y, Johansson E, Yang Y, Miller ML, Shen D, Orlicky DJ, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. (2010). Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis. J Hepatol 53: 1085-94.
  2. Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, Stringer KF, Wang B, Schneider SN, Nebert DW, Dalton TP. (2007). Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure. Hepatology 45: 1118-28.
  3. Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brustle A, Itsumi M, Jager C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. (2017). Glutathione Primes T Cell Metabolism for Inflammation. Immunity 46: 675-89.