Abcb11-flox Mouse

Abcb11, also known as BSEP (bile salt export pump), is a member of the ATP-binding cassette transporter family. It is located on the apical membrane of hepatocytes and mediates the secretion of bile salts from hepatocytes into the bile. This process is the rate-limiting step of bile salt secretion and the main driving force of bile flow, thus driving and maintaining the enterohepatic circulation of bile salts [2,3].

Mutations in Abcb11 can lead to various liver diseases. In children, it may cause progressive familial intrahepatic cholestasis type 2 (PFIC2), presenting as severe jaundice and liver dysfunction. For example, a homozygous Abcb11 mutation c.386G>A (p.C129Y) in a patient with PFIC2 led to impaired trafficking of BSEP to the plasma membrane, reduced cell-surface expression, and decreased bile acid transport [5]. In adults, Abcb11 variants are associated with pregnancy-associated liver dysfunction and acute/episodic cholestasis. The common variant p.Val444Ala in Abcb11 confers an increased risk of drug-induced liver injury and intrahepatic cholestasis of pregnancy (ICP) [1,4].

In conclusion, Abcb11 is crucial for bile salt secretion and maintaining the enterohepatic circulation. Genetic studies, especially those on mutations in Abcb11, have revealed its significant role in the development of various liver diseases in both children and adults, providing insights into the molecular mechanisms underlying these diseases and potential directions for treatment.