Detection of loci for allergic asthma using SMXA recombinant inbred strains of mice
Detection of loci for allergic asthma using SMXA recombinant inbred strains of mice
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DOI：
10.1007/s00251-012-0656-7
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发表时间：
2012
期刊：
影响因子：
3.2
通讯作者：
T. Ohno;M. Okamoto;T. Hara;N. Hashimoto;K. Imaizumi;M. Matsushima;M. Nishimura;K. Shimokata;Y. Hasegawa;T. Kawabe
中科院分区：
文献类型：
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作者：
T. Ohno;M. Okamoto;T. Hara;N. Hashimoto;K. Imaizumi;M. Matsushima;M. Nishimura;K. Shimokata;Y. Hasegawa;T. Kawabe
哮喘被认为是一种多因素的炎症性疾病，由于遗传易感个体对常见环境抗原的不适当免疫应答而引起。然而，精确的分子基础是未知的。为了鉴定对三种哮喘相关性状（气道高反应性（AHR）、嗜酸性粒细胞浸润和变应原特异性血清IgE水平）易感的基因，我们使用SMXA重组近交系（RI）小鼠进行了遗传分析。数量性状基因座分析检测到一个显着的位点上的17号染色体上的AHR。对于嗜酸性粒细胞浸润，在9号和16号染色体上检测到显著位点。虽然我们不能检测到任何显着的过敏原特异性血清IgE位点，分析consomic菌株显示，染色体17和19携带的基因，影响这一特点。我们检测了分别调节三种哮喘相关表型的遗传易感性位点。我们的研究结果表明，不同的遗传机制调节这些哮喘相关的表型。使用小鼠RI和consomic株的遗传分析增强了对人类哮喘分子机制的理解。
Asthma is regarded as a multifactorial inflammatory disorder arising as a result of inappropriate immune responses in genetically susceptible individuals to common environmental antigens. However, the precise molecular basis is unknown. To identify genes for susceptibility to three asthma-related traits, airway hyperresponsiveness (AHR), eosinophil infiltration, and allergen-specific serum IgE levels, we conducted a genetic analysis using SMXA recombinant inbred (RI) strains of mice. Quantitative trait locus analysis detected a significant locus for AHR on chromosome 17. For eosinophil infiltration, significant loci were detected on chromosomes 9 and 16. Although we could not detect any significant loci for allergen-specific serum IgE, analysis of consomic strains showed that chromosomes 17 and 19 carried genes that affected this trait. We detected genetic susceptibility loci that separately regulated the three asthma-related phenotypes. Our results suggested that different genetic mechanisms regulate these asthma-related phenotypes. Genetic analyses using murine RI and consomic strains enhance understanding of the molecular mechanisms of asthma in human.