胶原诱导性关节炎与 pristane 诱导性关节炎之间的比较基因分析。
A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis.
作者信息
Olofsson Peter, Lu Shemin, Holmberg Jens, Song Tusheng, Wernhoff Patrik, Pettersson Ulf, Holmdahl Rikard
机构信息
Section for Medical Inflammation Research, Sölvegatan 19, I11 BMC, Lund University, S-22184 Lund, Sweden.
出版信息
Arthritis Rheum. 2003 Aug;48(8):2332-42. doi: 10.1002/art.11100.
OBJECTIVE
To compare the genetic regulation of collagen-induced arthritis (CIA) with that of pristane-induced arthritis (PIA) in rats.
METHODS
A genome-wide linkage analysis of an (E3 x DA)DA backcross of rats with CIA (n = 364 male rats; the same strain combinations as previously used to determine the genetic control of PIA) was performed. The strongest loci in both CIA and PIA (i.e., Cia12/Pia4 and Cia13/Pia7) were isolated in congenic strains. Susceptibility in both congenic strains was tested in rats with CIA and in rats with PIA.
RESULTS
We found a striking, although not complete, similarity of the arthritis-controlling loci in CIA and in PIA, as well as the previously defined loci associated with cartilage destruction, antibody production, and the acute-phase response. All major PIA quantitative trait loci (QTLs) identified in early severe arthritis were also strong regulators of CIA. The 2 strongest QTLs, Cia12/Pia4 on chromosome 12 and Cia13/Pia7 on chromosome 4, were also analyzed in congenic strains with DA or E3 as the background genome. Consistent with the results of linkage analysis, the congenic strain experiments showed that the chromosome 4 locus was more penetrant in CIA than in PIA, while the chromosome 12 locus almost completely dominated the control of PIA severity.
CONCLUSION
The underlying genetic control of CIA was found to have many, but not all, pathogenic mechanisms in common with PIA, despite the use of a cartilage-specific antigen (type II collagen) to induce CIA but not PIA.
目的
比较大鼠胶原诱导性关节炎（CIA）与 pristane 诱导性关节炎（PIA）的基因调控。
方法
对患有 CIA 的大鼠（n = 364 只雄性大鼠；与先前用于确定 PIA 基因控制的相同品系组合）进行（E3×DA）DA 回交的全基因组连锁分析。在同源近交系中分离出 CIA 和 PIA 中最强的基因座（即 Cia12/Pia4 和 Cia13/Pia7）。在患有 CIA 和 PIA 的大鼠中测试这两种同源近交系的易感性。
结果
我们发现 CIA 和 PIA 中关节炎控制基因座存在显著但不完全相似之处，以及先前定义的与软骨破坏、抗体产生和急性期反应相关的基因座。在早期严重关节炎中鉴定出的所有主要 PIA 数量性状基因座（QTL）也是 CIA 的强调节因子。还在以 DA 或 E3 作为背景基因组的同源近交系中分析了 2 个最强的 QTL，即 12 号染色体上的 Cia12/Pia4 和 4 号染色体上的 Cia13/Pia7。与连锁分析结果一致，同源近交系实验表明，4 号染色体基因座在 CIA 中比在 PIA 中更具穿透性，而 12 号染色体基因座几乎完全主导了 PIA 严重程度的控制。
结论
尽管使用软骨特异性抗原（II 型胶原）诱导 CIA 而非 PIA，但发现 CIA 的潜在基因控制与 PIA 有许多（但并非全部）共同的致病机制。
Zotero 插件