Kawahito Y, Cannon G W, Gulko P S, Remmers E F, Longman R E, Reese V R, Wang J, Griffiths M M, Wilder R L
The Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892-1820, USA.
J Immunol. 1998 Oct 15;161(8):4411-9.
Adjuvant-induced arthritis (AIA) in rats is a widely used autoimmune experimental model with many features similar to rheumatoid arthritis (RA). To identify potential genetic regulatory mechanisms in RA, we conducted genome-wide linkage analysis in F2 progeny of arthritis-susceptible Dark Agouti (DA) and relatively resistant Fischer 344 (F344) inbred rats. We compared the data with our previously reported investigation of collagen-induced arthritis (CIA), which was expanded in the follow-up study reported in this work. We found two quantitative trait loci (QTLs) in common, i.e., Aia1/Cia1 on chromosome 20, which includes the MHC, and Aia3/Cia3 on chromosome 4. We also identified a second unique QTL in AIA, Aia2, on chromosome 4. Interestingly, the QTL region on chromosome 4 (Aia3/Cia3), like the MHC, appears to be involved in several other autoimmune diseases in rats, including insulin-dependent diabetes, thyroiditis, and experimental autoimmune uveitis. Moreover, an analysis of conserved synteny among rats, mice, and humans suggested that Aia2 and Aia3/Cia3, like Aia1/Cia1, contain candidate genes for several autoimmune/inflammatory diseases in mice and humans, including diabetes, systemic lupus erythematosus, inflammatory bowel disease, asthma/atopy, multiple sclerosis, and RA. The rat models appear to provide a powerful complementary approach to identify and characterize candidate genes that may contribute to autoimmune diseases in several species.
大鼠佐剂性关节炎（AIA）是一种广泛应用的自身免疫性实验模型，具有许多与类风湿关节炎（RA）相似的特征。为了确定RA潜在的遗传调控机制，我们对关节炎易感的黑褐大鼠（DA）和相对抗性的Fischer 344（F344）近交系大鼠的F2后代进行了全基因组连锁分析。我们将这些数据与我们之前报道的胶原诱导性关节炎（CIA）研究数据进行了比较，本研究中的后续研究对该数据进行了扩展。我们发现了两个共同的数量性状基因座（QTL），即20号染色体上的Aia1/Cia1，其中包括主要组织相容性复合体（MHC），以及4号染色体上的Aia3/Cia3。我们还在AIA中确定了4号染色体上的第二个独特QTL，即Aia2。有趣的是，4号染色体上的QTL区域（Aia3/Cia3）与MHC一样，似乎与大鼠的其他几种自身免疫性疾病有关，包括胰岛素依赖型糖尿病、甲状腺炎和实验性自身免疫性葡萄膜炎。此外，对大鼠、小鼠和人类之间保守同线性的分析表明，Aia2和Aia3/Cia3与Aia1/Cia1一样，包含小鼠和人类几种自身免疫/炎症性疾病的候选基因，包括糖尿病、系统性红斑狼疮、炎症性肠病、哮喘/特应性、多发性硬化症和RA。大鼠模型似乎为鉴定和表征可能导致几种物种自身免疫性疾病的候选基因提供了一种强大的补充方法。
