Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Curr Opin Gastroenterol. 2010 May;26(3):274-9. doi: 10.1097/MOG.0b013e32833755aa.
Primary biliary cirrhosis (PBC) is a human autoimmune liver disease whose molecular pathogenesis is poorly understood because of the difficulty in accessing human tissue and the absence of appropriate animal models. Recently, several unique murine models of human PBC have been discovered. These models have great potential for illustrating the cause and the cellular events that lead to biliary-specific damage. The purpose of this review is to summarize recent progress in these models.
The murine models of autoimmune cholangitis include the transforming growth factor beta receptor II (TGF-betaRII) dominant-negative (dnTGF-betaRII), IL-2 receptor alpha deleted (IL-2Ralpha-/-), scurfy, nonobese diabetic (NOD) c3c4, and Ae2 gene-disrupted (Ae2a,b-/-) mice. Recently, we have also established a successful murine model following the immunization with a chemical mimicry of the lipoyl-lysine residue of the E2 component of PDC-E2.
These emerging murine models have greatly enabled researchers to address the pathogenesis of human PBC and to elucidate pathogenic factors. These models will ultimately lead to new therapeutic options for human PBC.
原发性胆汁性肝硬化（PBC）是一种人类自身免疫性肝病，由于难以获取人类组织和缺乏合适的动物模型，其分子发病机制仍不清楚。最近，发现了几种独特的人类 PBC 小鼠模型。这些模型对于阐明导致胆管特异性损伤的原因和细胞事件具有巨大的潜力。本文综述的目的是总结这些模型的最新进展。
自身免疫性胆管炎的小鼠模型包括转化生长因子-β受体 II（TGF-βRII）显性负（dnTGF-βRII）、白细胞介素-2 受体α缺失（IL-2Ralpha-/-）、scurfy、非肥胖型糖尿病（NOD）c3c4 和 Ae2 基因缺失（Ae2a,b-/-）小鼠。最近，我们还成功建立了一种通过免疫化学模拟 PDC-E2 的 E2 成分的赖氨酸残基的新型小鼠模型。
这些新兴的小鼠模型极大地帮助研究人员了解人类 PBC 的发病机制，并阐明致病因素。这些模型最终将为人类 PBC 带来新的治疗选择。
