Contribution of genetic studies in rodent models of autoimmune arthritis to understanding and treatment of rheumatoid arthritis.
Contribution of genetic studies in rodent models of autoimmune arthritis to understanding and treatment of rheumatoid arthritis.
复制标题
自身免疫性关节炎啮齿动物模型的遗传学研究对理解和治疗类风湿性关节炎的贡献。
DOI：
10.1038/sj.gene.6364419
复制
发表时间：
2007
影响因子：
5
通讯作者：
Gulko,PS
中科院分区：
文献类型：
--
作者：
Gulko,PS
风湿性关节炎（RA）是一种慢性的、潜在的使人衰弱的自身免疫性疾病。虽然近年来出现了新的治疗方法，但很少能达到疾病缓解。RA是一种复杂的性状，其易感性和严重性基因的鉴定有望产生新的治疗干预靶点。然而，找到这些基因并了解它们的功能一直是一项具有挑战性的任务。研究啮齿动物的杂交和近亲繁殖产生的近交系已成为一个重要的补充战略，以确定关节炎基因，并了解他们如何运作，以调节疾病。此外，这些新的啮齿动物关节炎基因将成为治疗干预的新靶点，并将为RA的相关研究确定新的候选基因或候选途径。在这篇评论意见文章中，我讨论了RA遗传学，基因鉴定中的困难，以及啮齿动物模型如何促进（1）关节炎易感性和严重性基因的发现，（2）基因-环境相互作用的研究，（3）基因-性别相互作用的研究，（4）上位性，（5）特定基因的功能表征，（6）开发新的治疗方法和（7）从啮齿动物研究中产生的信息如何有助于理解和潜在地治疗RA。
Rheumatoid arthritis (RA) is a chronic and potentially debilitating autoimmune disease. While novel therapies have emerged in recent years, disease remission is rarely achieved. RA is a complex trait, and the identifying of its susceptibility and severity genes has been anticipated to generate new targets for therapeutic intervention. However, finding those genes and understanding their function has been a challenging task. Studies in rodent intercrosses and congenics generated from inbred strains have been an important complementary strategy to identify arthritis genes, and understand how they operate to regulate disease. Furthermore, these new rodent arthritis genes will be new targets for therapeutic interventions, and will identify new candidate genes or candidate pathways for association studies in RA. In this review-opinion article I discuss RA genetics, difficulties involved in gene identification, and how rodent models can facilitate (1) the discovery of both arthritis susceptibility and severity genes,(2) studies of gene–environment interactions,(3) studies of gene–gender interactions,(4) epistasis,(5) functional characterization of the specific genes,(6) development of novel therapies and (7) how the information generated from rodent studies will be useful to understanding and potentially treating RA.