title: Animal models of primary biliary cirrhosis.
abstract: Within the last decade, several mouse models that manifest characteristic features of primary biliary cirrhosis (PBC) with antimitochondrial antibodies (AMAs) and immune-mediated biliary duct pathology have been reported. Here, the authors discuss the current findings on two spontaneous (nonobese diabetic autoimmune biliary disease [NOD.ABD] and dominant negative transforming growth factor-β receptor II [dnTGFβRII]) and two induced (chemical xenobiotics and microbial immunization) models of PBC. These models exhibit the serological, immunological, and histopathological features of human PBC. From these animal models, it is evident that the etiology of PBC is multifactorial and requires both specific genetic predispositions and environmental insults (either xenobiotic chemicals or microbial), which lead to the breaking of tolerance and eventually liver pathology. Human PBC is likely orchestrated by multiple factors and hence no single model can fully mimic the immunopathophysiology of human PBC. Nevertheless, knowledge gained from these models has greatly advanced our understanding of the major immunological pathways as well as the etiology of PBC.
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California.
authors: Jinjun
authors: J
authors: Wang
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California.
authors: Guo-Xiang
authors: GX
authors: Yang
authors: Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan.
authors: Koichi
authors: K
authors: Tsuneyama
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California.
authors: M Eric
authors: ME
authors: Gershwin
authors: Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: William M
authors: WM
authors: Ridgway
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California.
authors: Patrick S C
authors: PS
authors: Leung
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001653:Bile Ducts, Intrahepatic / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D042301:Sphingomonadaceae / Q000472:pathogenicity; D015262:Xenobiotics
chemical_list: D015415:Biomarkers; D018125:Receptors, Transforming Growth Factor beta; D015262:Xenobiotics; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II