Gclm/Nrf2 DKO (Gclm−/−/Nrf2−/−) strain
In examining the effects of GSH effects on alcohol metabolism, Nrf2 was shown to be up-regulated in Gclm−/− mice by ethanol treatment (1). In a state of chronic GSH depletion, the Keap1-Nrf2-ARE signaling pathway appears necessary for the paradoxical resilience to ethanol-induced liver toxicity (2). Nrf2 KO mice are highly sensitive to ethanol toxicity and have increased morbidity and mortality upon ethanol treatment (3). We have cross-bred Nrf2 KO mice with the Gclm KO mice and have preliminary data that suggests that the resultant Nrf2/Gclm DKO mice experience more hepatitis than either Gclm KO or wild-type mice (Fig. 1). These DKO mice are viable and reach maturity; however, they have yet to produce progeny.
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