Overexpression of the bile salt export pump (ABCB11) in ABCB4-deficient mice aggravates liver fibrosis

Aims: The three biliary lipids are excreted into bile by three ATP-dependent transporters: ABCB4 translocates phosphatidylcholine, ABCB11 exports bile acids, and ABCG5/G8 carry cholesterol. ABCB4-deficient mice develop secondary biliary fibrosis gradually due to regurgitation of bile acids from leaky bile ducts. We have generated Abcb11 transgenic mice, which display isolated bile acid hypersecretion into bile (Wang et al. Eur J Clin Invest 2010; in press). Hence, we hypothesized that ABCB11 overexpression should aggravate the biliary phenotype of ABCB4-deficient mice. Methods: ABCB4-deficient mice were crossed…