Analysis of candidate genes of spontaneous arthritis in mice deficient for interleukin-1 receptor antagonist
Analysis of candidate genes of spontaneous arthritis in mice deficient for interleukin-1 receptor antagonist
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白细胞介素1受体拮抗剂缺陷小鼠自发性关节炎候选基因分析
DOI：
10.1266/ggs.87.107
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发表时间：
2012-04-01
影响因子：
1.1
通讯作者：
Jiao, Yan
中科院分区：
文献类型：
--
作者：
Cao, Yanhong;Li, Caijuan;Jiao, Yan
在此之前，我们在小鼠1号染色体上发现了一个主要的数量性状位点（QTL），该位点调节由易患关节炎的BALB/c和缺乏白细胞介素-1受体拮抗剂的抗关节炎的DBA/1小鼠产生的F2群体对关节炎的易感性。为了进一步选择QTL的候选基因，我们分析了38个F2个体关节炎的表达模式，并比较了关键候选基因与亲本菌株的表达水平。在38只F2小鼠中发现了两个不同的关节炎小鼠亚群。一组患病小鼠的特点是髓系细胞显性炎症，而另一组主要与炎症细胞抗凋亡活性增加有关。亲本菌株在QTL区域的几个差异表达的重要候选基因与髓细胞、凋亡活性或两者相关。这些基因中约有四分之一曾在文献中与关节炎有关。目前的研究揭示了由于白细胞介素-1受体拮抗剂缺乏而导致的自发性关节炎小鼠的两个不同亚群，这表明与骨髓细胞和/或凋亡活性相关的功能基因最有可能是QTL的关键候选基因。
Previously, we identified a major quantitative trait locus (QTL) on mouse chromosome 1 that regulates the susceptibility to arthritis in an F2 population generated from arthritis-prone BALB/c and arthritis-resistant DBA/1 mice deficient for interleukin-1 receptor antagonist. To further select candidate genes for the QTL, we analyzed the expression patterns of arthritis in 38 F2 individuals and compared the expression levels of key candidate genes to the parental strains. Two distinct subpopulations of arthritic mice were identified in the 38 F2 mice. One subgroup of diseased mice was characterized by myeloid cell dominant inflammation, whereas the other was mainly associated with increased anti-apoptotic activities of inflammatory cells. Several differentially expressed important candidate genes in parental strains in the QTL region are relevant to myeloid cell, apoptotic activities, or to both. About one-quarter of those genes have been previously linked to arthritis in literature. The present study reveals two distinct subpopulations of arthritic mice with spontaneous arthritis due to deficiency for interleukin-1 receptor antagonist, suggesting that genes with function relevant to myeloid cell and/or apoptotic activities are most likely the key candidate genes for the QTL.