Attempt of producing an experimental animal model of biliary atresia using bcl-2 knock-out mice : the analysis of bcl-2 as the apoptosis inhibitor in biliary atresia

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As the expression of the bcl-2 gene is analyzed by using the liver biopsy sample at the time of the operation for biliary atresia it has become clear that lower expression of the bcl-2 gene in the liver specimen from patients with biliary atresia than those from controls. Thereupon, we tried to study the liver disease of biliary atresia using the bcl-2 knock-out mouse.Bcl-2 knock-out mice did not survive long enough to be appropriately evaluated. We paid attention to the inv variant mouse that happens to be complicated by cholestasis as well as situs inversus. Furthermore we are studying inv status in biliary atresia patients associated with situs inversus using their blood samples. These studies should elucidate the role of apoptosis inhibitory genes and inv genes in the pathogenesis of biliary atresia.Abnormally progressed apoptosis resulting in diffuse cholangitis would lead to inflammatory catastrophe all over the liver. We already disclosed the significant roles of the various kinds of fibrinogenic cytokines, mast cell, c-kit, and CD14 in the inflammatory process in biliary atresia. While hepatocytes and intrahepatic bile ducts can regenerate enough during and immediately after the embryonal period even when they are severely damaged, extrahepatic biliary atresia is irreversible. We hypothesized that biliary atresia is ultimately established in these process above