Gulko P S, Kawahito Y, Remmers E F, Reese V R, Wang J, Dracheva S V, Ge L, Longman R E, Shepard J S, Cannon G W, Sawitzke A D, Wilder R L, Griffiths M M
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA.
Arthritis Rheum. 1998 Dec;41(12):2122-31. doi: 10.1002/1529-0131(199812)41:12<2122::AID-ART7>3.0.CO;2-#.
To identify novel non-major histocompatibility complex (non-MHC) genetic loci controlling the severity of homologous rat type II collagen-induced arthritis (CIA).
We conducted a genome-wide scan to identify CIA regulatory quantitative trait loci (QTL) in an F2 cross between DA (CIA highly susceptible) and ACI (CIA resistant) inbred rats immunized with homologous rat type II collagen (RII). These strains share the MHC/RT1av1 haplotype required for susceptibility to RII-induced CIA.
F2 females had higher median arthritis scores than did males. Relative resistance in the males was determined by inheriting either a DA or an ACI Y chromosome and was independent of the source of the X chromosome. In addition, a major QTL was localized on chromosome 2 (Cia7, logarithm of odds score 4.6). Cia7 is in a region that shows linkage conservation with chromosomal regions that regulate autoimmune diabetes and experimental autoimmune encephalomyelitis in mice and multiple sclerosis in humans.
Sex chromosomes and Cia7 play an important role in regulating CIA in response to RII. This rat model should facilitate positional cloning and functional characterization of regulatory genes that may play a role in several forms of autoimmune disease, including rheumatoid arthritis.
鉴定控制同源大鼠II型胶原诱导性关节炎（CIA）严重程度的新型非主要组织相容性复合体（非MHC）基因座。
我们进行了全基因组扫描，以鉴定在用同源大鼠II型胶原（RII）免疫的DA（CIA高度易感）和ACI（CIA抗性）近交系大鼠之间的F2杂交后代中CIA调控数量性状基因座（QTL）。这些品系共享对RII诱导的CIA易感性所需的MHC/RT1av1单倍型。
F2雌性大鼠的关节炎中位数评分高于雄性。雄性大鼠的相对抗性由继承DA或ACI Y染色体决定，且与X染色体来源无关。此外，一个主要的QTL定位于2号染色体上（Cia7，优势对数分数为4.6）。Cia7所在区域与调节小鼠自身免疫性糖尿病和实验性自身免疫性脑脊髓炎以及人类多发性硬化症的染色体区域具有连锁保守性。
性染色体和Cia7在响应RII调节CIA中起重要作用。该大鼠模型应有助于对可能在包括类风湿性关节炎在内的多种自身免疫性疾病形式中发挥作用的调控基因进行定位克隆和功能表征。
