Abstract 688 Gastroenterology and Nutrition Platform, Monday, 5/3

Extrahepatatic biliary atresia (BA) is a devastating disease of the neonate in which the hepatic and/or common bile duct is obliterated or interrupted. Infants and children with this diagnosis constitute 50-60% of the pediatric population that undergoes orthotopic liver transplantation. However, there is still very little known about the etiology and pathogenisis of BA. Several recent studies have demonstrated that the anomalies of situs determination are more commonly associated with BA than previously recognized. In this study we examined the pathogenesis of jaundice in the inv mouse, a transgenic mouse in which a recessive deletion of the inversin gene results in situs inversus and jaundice. The results show that these mice have cholestatis with conjugated hyperbilirubinemia, failure to excrete technicium-labelled mebrofenin from the liver into the small intestine, lack of continuity between the biliary tree and the small intestine as demonstrated by trypan blue cholangiography, and a liver histological picture indicative of extrahepatatic biliary obstruction with negligible inflammation/necrosis within the hepatic parenchyma. Lectin histochemical staining of biliary epithelial cells in serial sections suggests the presence of several different anomalies of the extrahepatatic biliary system. These results suggest that the inversin gene plays a role in the morphogenesis of the hepatobiliary system and raise the possibility that alterations in the human orthologue of inversin account for the etiology of a subgroup of cases of BA in which there are also anomalies of situs determination.