Hepatocyte-specific Gclch/h knockout strain
The Gclch/h mouse line was created by crossing Gclcf/f and Alb-Cre mice (1). Gclch/h mice experience almost complete loss of hepatic GSH (5% of normal) and die from acute liver failure when mitochondrial failure occurs. Chronic administration of N-acetyl-cysteine, a treatment that promotes only a mild increase in liver GSH levels (to 8% of normal) but partially preserves mitochondrial function, allows Gclch/h mice to survive to adulthood, albeit with the still serious liver fibrosis and cirrhosis (2). Gclch/h mice demonstrate liver pathologies reminiscent of those occurring at the various clinical stages of alcoholic liver disease.
- 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.
- 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.