Division of Experimental Animals, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Immunogenetics. 2013 Jan;65(1):17-24. doi: 10.1007/s00251-012-0656-7. Epub 2012 Oct 19.
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.
哮喘被认为是一种多因素炎症性疾病,是由于遗传易感个体对常见环境抗原产生不适当的免疫反应而引起的。然而,其确切的分子基础尚不清楚。为了鉴定与三种哮喘相关特征(气道高反应性(AHR)、嗜酸性粒细胞浸润和过敏原特异性血清 IgE 水平)相关的易感性基因,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 AHR 的一个显著染色体 17 位。对于嗜酸性粒细胞浸润,在染色体 9 和 16 上检测到显著的位。虽然我们不能检测到过敏原特异性血清 IgE 的任何显著位,但对同源染色体系的分析表明,染色体 17 和 19 携带影响该特征的基因。我们检测到了分别调节三种哮喘相关表型的遗传易感性位。我们的结果表明,不同的遗传机制调节这些哮喘相关表型。使用鼠 RI 和同源染色体系的遗传分析增强了对人类哮喘分子机制的理解。