An additional heme oxygenase-1 knockout increases systemic inflammation and fibrosis in MDR2 knockout mice

Background: Deletion of the multi drug resistance protein 2 (Mdr2) in mice causes hepatic inflammation and fibrosis with progression to hepatocellular carcinoma (HCC) at about 12 month of age (Mdr2 knockout mouse; Mdr2ko; FVB.129P2-Abcb4tm1Bor). We have recently shown that induction of heme oxygenase-1 (HO-1) in Mdr2ko mice interferes with liver inflammation, fibrosis formation and proliferation. We now established a double knockout mouse for Mdr2 and HO-1 (Mdr2/HO-1ko) to further investigate effects of HO-1 on chronic inflammation of the liver and its consequences. Methods: Liver damage was monitored by alanin…