The mechanism of biliary lipid secretion and its defects

Biliary lipid secretion is an important physiological event; not only for t he disposal of cholesterol from the body but also for the protection of cel ls lining the biliary tree against bile salts. Insight into the (patho)phys iological role of biliary lipid secretion has been recently expanded throug h the study of a generation of mice with a disruption of the Mdr2 gene, who do not secrete lipids into bile. Mdr2 P-glycoprotein translocates phosphol ipids across the hepatocanalicular membrane. These animals suffer from prog ressive Liver disease caused by the toxic detergent action of bile salts. V ery recently, it has become clear that an analogous inherited human Liver d isease exists, which is caused by the absence of biliary lipid secretion. P atients with this disease, Progressive Familial Intrahepatic Cholestasis (P FIC) type 3, have a mutation in the MDR3 gene, which is the human homologue of the murine Mdr2 gene.