Leung Patrick S C, Yang Guo Xiang, Dhirapong Amy, Tsuneyama Koichi, Ridgway William M, Gershwin M Eric
Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA, USA.
Methods Mol Biol. 2012;900:291-316. doi: 10.1007/978-1-60761-720-4_14.
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.
原发性胆汁性肝硬化（PBC）是一种以女性为主的肝脏自身免疫性疾病，其特征为肝内胆管的免疫介导性破坏以及抗线粒体抗体（AMA）的存在。由于获取人体组织存在困难且缺乏合适的动物模型，在理解该疾病的分子发病机制方面进展有限。最近，已经描述了几种表现出与人类PBC相似的血清学、生化和组织学特征的独特小鼠模型。在本文中，我们讨论了关于三种自发性和两种诱导性PBC小鼠模型的当前数据。自发性模型包括：（a）NOD.c3c4，（b）显性负性转化生长因子-β受体II（dnTGFβRII），以及（c）IL-2Rα（-/-）小鼠品系模型。两种诱导性模型包括：（a）异生素诱导型和（b）芳香新鞘氨醇免疫小鼠。这些动物模型为进一步研究PBC的病因和发病机制提供了各种重要平台。描述了用于评估这些动物模型的实验室方法和方案。最后，我们强调认识到动物模型的优势和局限性对于数据分析及其在治疗研究中的应用至关重要。
