Experimental Models of Lupus Nephritis
Experimental Models of Lupus Nephritis
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DOI：
10.1159/000319241
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Grande, Joseph P.
中科院分区：
文献类型：
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作者：
Grande, Joseph P.
许多小鼠模型概括了系统性红斑狼疮的许多特征。自发性狼疮模型为基因连锁研究提供了基础，以确定易感小鼠患肾炎风险增加的基因座。通过使用携带候选基因的定向缺失或过度表达的转基因小鼠，已经验证了易感基因内的基因的功能相关性。关键的基因靶点涉及自身抗原的产生、刺激B细胞产生自身抗体、刺激T细胞提供B细胞帮助以及免疫复合体组织沉积后的细胞因子介导的损伤。在这篇综述中，我们回顾了人类狼疮性肾炎常用模型的特点。本文还讨论了在这些模型中寻找与狼疮性肾炎发病和进展相关的候选基因的策略。最后，总结了验证靶基因作为狼疮性肾炎的病理生理相关介质的关键研究，以及确定潜在的治疗干预靶点的研究。版权所有(C)2011 S.Karger AG，巴塞尔
A number of murine models recapitulate many of the features of systemic lupus. Spontaneous models of lupus have provided the basis for genetic linkage studies to define loci that confer an increased risk of nephritis in susceptible mice. Functional relevance of genes within susceptibility loci have been verified through the use of transgenic mice bearing targeted deletions or overexpression of candidate genes. Critical gene targets are involved in the production of autoantigens, stimulation of B cells to produce autoantibodies, stimulation of T cells to provide B cell help and cytokine-mediated damage following tissue deposition of immune complexes. In this overview, features of the commonly employed models of human lupus nephritis are reviewed. Strategies to identify candidate genes involved in the initiation and progression of lupus nephritis in these models are discussed. Finally, key studies to validate target genes as pathophysiologically relevant mediators of lupus nephritis and studies to identify potential targets for therapeutic intervention are summarized. Copyright (C) 2011 S. Karger AG, Basel