Research Unit for Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Graz, Austria.
Clin Rev Allergy Immunol. 2015 Jun;48(2-3):207-17. doi: 10.1007/s12016-014-8442-y.
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated cholangiopathies with enigmatic etiology and pathogenesis. They have distinct clinical, laboratory, immunological, and histomorphological characteristics. Well-characterized animal models for PBC and PSC are utterly needed to develop novel pathogenetic concepts and to study innovative treatment strategies. The aim of the current paper is to outline the characteristics of ideal PBC and PSC animal models and to contrast this with a real-life up-to-date overview of currently available mouse models. Although some of this models show several individual characteristics of PBC and PSC, it is obvious that all of them have substantial and important limitations. Nevertheless, some may be beneficial to study certain pathophysiological aspects. Potential cholangiopathy animal models should be systematically investigated in regard to elevated serum alkaline phosphatase, bilirubin, and bile acid levels; immunological abnormalities; and longitudinal studies in regard to their liver phenotype. We herein propose a common systematic workup for potential models based on the fact that there are some intriguing disease combinations in specific genetically modified mice and recommend a stepwise process in regard to model characterization with methodical harvesting and screening of numerous organs for potential concomitant diseases. Due to the complex nature of both cholangiopathies, it seems to be very likely that no single perfect PBC or PSC model will ever be generated. The models outlined herein will certainly help to clarify specific pathogenetic aspects and even more important may turn out to be suitable to test potential drugs for treatment.
原发性胆汁性胆管炎 (PBC) 和原发性硬化性胆管炎 (PSC) 是具有神秘病因和发病机制的免疫介导性胆管病。它们具有独特的临床、实验室、免疫学和组织形态学特征。迫切需要为 PBC 和 PSC 开发特征明确的动物模型，以提出新的发病机制概念并研究创新的治疗策略。本文旨在概述理想的 PBC 和 PSC 动物模型的特征，并将其与当前可用的小鼠模型的最新实际情况进行对比。尽管其中一些模型显示出 PBC 和 PSC 的一些个别特征，但显然它们都存在重大且重要的局限性。尽管如此，其中一些模型可能有助于研究某些病理生理方面。应根据血清碱性磷酸酶、胆红素和胆汁酸水平升高、免疫异常以及针对其肝表型的纵向研究，系统性地研究潜在的胆管病动物模型。我们在此提出了一种基于特定基因修饰小鼠中存在一些有趣疾病组合的潜在模型的常见系统评估，并建议针对模型特征进行逐步处理，对多个器官进行有针对性的采集和筛选，以发现潜在的伴随疾病。由于这两种胆管病的复杂性，似乎不太可能会生成单一的完美 PBC 或 PSC 模型。本文中概述的模型肯定有助于阐明特定的发病机制方面，甚至更重要的是，可能适合测试用于治疗的潜在药物。
