title: Animal models of primary biliary cirrhosis: materials and methods.
abstract: Primary biliary cirrhosis (PBC) is a female-predominant autoimmune disease of the liver characterized by immune-mediated destruction of the intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMAs). There have been limited advances in understanding the molecular pathogenesis of the disease because of the difficulty in accessing human tissues and the absence of appropriate animal models. Recently, several unique murine models that manifest the serological, biochemical, and histological features similar to human PBC have been described. In this article, we discuss the current data on three spontaneous and two induced murine models of PBC. The spontaneous models are: (a) NOD.c3c4, (b) dominant negative TGF-β receptor II (dnTGFβRII), and (c) IL-2Rα(-/-) mouse line models. The two induced models are: (a) xenobiotic and (b) Novosphingobium aromaticivorans immunized mice. These animal models provide various important platforms to further investigate the etiology and mechanisms of pathogenesis in PBC. Laboratory methodologies and the protocols that are used in evaluating these animal models are described. Finally, we stress the importance of realizing the strengths and limitations of the animal models are essential in data analysis and their application in therapeutic studies.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA, USA. psleung@ucdavis.edu
authors.forename: Patrick S C
authors.initials: PS
authors.lastname: Leung
authors.forename: Guo Xiang
authors.initials: GX
authors.lastname: Yang
authors.forename: Amy
authors.initials: A
authors.lastname: Dhirapong
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: William M
authors.initials: WM
authors.lastname: Ridgway
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018925:Chemokines / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000276:immunology; D008967:Molecular Biology / Q000379:methods*; D016612:Paraffin Embedding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D013154:Spleen / Q000473:pathology; D013194:Staining and Labeling
chemical_list: D001324:Autoantigens; D018925:Chemokines; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II