Identification of a quantitative trait locus for ileitis in a spontaneous mouse model of Crohn's disease: SAMP1/YitFc
Identification of a quantitative trait locus for ileitis in a spontaneous mouse model of Crohn's disease: SAMP1/YitFc
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DOI：
10.1016/s0016-5085(03)00876-x
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发表时间：
2003-08-01
期刊：
影响因子：
29.4
通讯作者：
McDuffie, M
中科院分区：
文献类型：
--
作者：
Kozaiwa, K;Sugawara, K;McDuffie, M
背景和目的：SAMP 1/Yit小鼠品系发生具有克罗恩病组织学特征的自发性回肠炎。SAMP 1/YitFc亚系（SAMP 1/Fc）中的疾病表达通过与C57 BL/6 J（B6）小鼠异交而部分抑制，表明疾病易感性的复杂遗传控制具有显性和隐性决定因素。我们对（B6 x SAMP 1/Fc）F-2杂交进行了遗传分析，以定位该模型中调节肠道炎症的基因。方法：全基因组扫描进行了一个小组的微卫星位点确定为信息的这种交叉。使用Map Manager QT使用序列回归方法识别数量性状基因座。在基因组水平上对位置候选基因进行选择性测序，以确定潜在的易感基因进行功能筛选。结果如下：对（B6 x SAMP 1/Fc）F2小鼠进行全基因组扫描，在可能遗传自AKR小鼠品系的区域中，在9号染色体上发现了一个SAMP衍生的数量性状基因座，该基因座具有加性效应。候选区间包含几个感兴趣的基因，因为它们在免疫系统功能、肠上皮功能或两者中的潜在作用。在6号染色体和X染色体上也观察到了其他位点的暗示性证据。结论：SAMP 1/Fc等位基因的一个位点，命名为Ibdq 1，促进炎症相关的上皮损伤在这些小鼠。与（B6 x SAMP 1/Fc）F-1小鼠中持续性轻度回肠炎一致，该基因座似乎以累加方式起作用。在这个区间中的两个基因，编码白细胞介素10受体α链和白细胞介素：18，是Ibdq 1的极好候选者。
Background & Aims: The SAMP1/Yit mouse strain develops spontaneous ileitis with histologic features of Crohn's disease. Disease expression in the SAMP1/YitFc subline (SAMP1/Fc) is partially inhibited by outcross to C57BL/6J (B6) mice, suggesting complex genetic control of disease susceptibility with both dominant and recessive determinants. We performed a genetic analysis of a (B6 x SAMP1/Fc)F-2 cross to localize the genes regulating intestinal inflammation in this model. Methods: A genome-wide scan was performed using a panel of microsatellite loci determined to be informative for this cross. Quantitative trait loci were identified with Map Manager QT using a serial regression approach. Positional candidate genes were selectively sequenced at the genomic level to identify potential susceptibility genes for functional screening. Results: A genome-wide scan of (B6 x SAMP1/Fc)F2 mice identified a SAMP-derived quantitative trait loci with additive effects on chromosome 9 in a region likely to have been inherited from the AKR mouse strain. The candidate interval contains several genes of interest because of their potential role in either immune system function, intestinal epithelial function, or both. Suggestive evidence for additional loci was also observed on chromosomes 6 and X. Conclusions: The SAMP1/Fc allele for a locus, designated Ibdq1, promotes inflammation-associated epithelial damage in these mice. Consistent with persistent mild ileitis in (B6 x SAMP1/Fc)F-1 mice, this locus appears to function in an additive fashion. Two genes in this interval, encoding the interleukin 10 receptor alpha chain and interleukin :18, are excellent candidates for Ibdq1.