Effect of liver-specific deletion of Gclc, Nrf2, and Gclc-Nrf2 on the liver

The rate-limiting step in glutathione (GSH) synthesis is controlled by glutamate-cysteine ligase catalytic subunit. GSH is reported to buffer oxidative stress. In the absence of GSH, the antioxidant transcription factor Nrf2 is reported to be stabilized. The liver has the highest levels of GSH, but its impact on liver homeostasis is unclear. To investigate this, we induced a liver-specific deletion of Gclc (Gclc f/f), Nrf2 (Nrf2 f/f), or Gclc-Nrf2 (Gclc f/f Nrf2 f/f) by injecting my via tail-vein with AAV-TBG-Cre, which induces recombination specifically in hepatocytes. Gclc wt/wt (Control), Gclc f/f, Nrf2 f/f, and Gclc f/f Nrf2 f/f were injected via tail-vein with 2.5e11 pfu of AAV-TBG-Cre. Three weeks following injection with AAV-TBG-Cre, mice were sacrifice and liver was harvested for RNA analysis.