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.

1. 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.
2. 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.