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Animal Models of Primary Biliary Cirrhosis: Materials and Methods

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Autoimmunity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 900))

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.

Supported in part by National Institutes of Health grants DK074768 DK090019, DK067003, and DK39588.

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Abbreviations

PBC:

Primary biliary cirrhosis

AMA:

Antimitochondrial antibody

PDC-E2:

E2 subunits of pyruvate dehydrogenase

BCOADC-E2:

2-Oxo acid dehydrogenase

OGDC-E2:

2-Oxo-glutarate dehydrogenase

NOD:

Non-obese diabetic

dnTGFβRII:

Dominant negative TGF-β receptor II

IDDM:

Insulin-dependent diabetes mellitus

BSA:

Bovine serum albumin

2-OA:

2-Octynoic acid

NKT:

Natural killer T cells

MHC:

Major histocompatibility complex

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Authors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA, USA

    Patrick S. C. Leung, Guo Xiang Yang, Amy Dhirapong & M. Eric Gershwin

  2. Department of Pathology, University of Toyama, Toyama, Japan

    Koichi Tsuneyama

  3. Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    William M. Ridgway

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  1. Patrick S. C. Leung
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  2. Guo Xiang Yang
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  3. Amy Dhirapong
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  4. Koichi Tsuneyama
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  5. William M. Ridgway
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  6. M. Eric Gershwin
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Correspondence to Patrick S. C. Leung .

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  1. College of Medicine, Division of Rheumatology, State University of New York, UMU, East Adams St. 750, Syracuse, 13210, New York, USA

    Andras Perl

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Leung, P.S.C., Yang, G.X., Dhirapong, A., Tsuneyama, K., Ridgway, W.M., Gershwin, M.E. (2012). Animal Models of Primary Biliary Cirrhosis: Materials and Methods. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Biology, vol 900. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-720-4_14

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  • DOI: https://doi.org/10.1007/978-1-60761-720-4_14

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