Animal Models of Primary Biliary Cirrhosis

Jinjun Wang; Guo-Xiang Yang; Koichi Tsuneyama; M. Eric Gershwin; William M. Ridgway; Patrick S.C. Leung

doi:10.1055/s-0034-1383728

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2014; 34(03): 285-296
DOI: 10.1055/s-0034-1383728

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Animal Models of Primary Biliary Cirrhosis

Jinjun Wang

¹Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California

²College of Environmental Science and Engineering, Yangzhou University, Yangzhou, Jaingsu Province, China

,

Guo-Xiang Yang

¹Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California

,

Koichi Tsuneyama

³Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan

,

M. Eric Gershwin

¹Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California

,

William M. Ridgway

⁴Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio

,

Patrick S.C. Leung

¹Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California

› Author Affiliations

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.

Keywords

antimitochondrial antibodies - cholangiocytes - dnTGFBRII - intrahepatic bile ducts - NOD.ABD - xenobiotics - microbial immunization

Full Text

References

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