Animal Models for Primary Biliary Cirrhosis

Abstract

Primary biliary cirrhosis (PBC) is a liver specific autoimmune disease characterized by antimitochondrial autoantibodies (AMAs) and progressive destruction of intrahepatic bile ducts. The elucidation of early events in the induction of tissue inflammation and autoimmunity in PBC has been hampered by the cryptic onset of the disease, the practical limitations in accessing human liver and the lack of a suitable animal model. Three spontaneous autoimmune biliary disease (ABD) mouse models, including NOD.c3c4 and NOD.c3c4-derived, dominant negative TGF-β receptor II (dnTGFβRII), and IL-2Rα −/− mouse models have been reported recently. All of these spontaneous ABD animal models for PBC develop features characteristic of human PBC, including biliary lymphocytic infiltrates, AMAs directed against the inner lipoyl domain of the E2 subunits of the pyruvate dehydrogenase complex (PDC-E2), and elevated serum levels of IFN-γ and TNF-α. Although some differences exist, these models provide important tools to study the genetic basis and the role of immunoregulation in autoimmune cholangitis and also to allow observation of the earliest stages of loss of tolerance.