Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice
Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice
复制标题
DOI：
10.1165/ajrcmb.23.4.4199
复制
发表时间：
2000-10-01
影响因子：
6.4
通讯作者：
Wills-Karp, M
中科院分区：
文献类型：
--
作者：
Ewart, SL;Kuperman, D;Wills-Karp, M
临床表型的变异性、不受控制的环境影响和遗传异质性阻碍了人类哮喘潜在遗传位点的鉴定。为了避免这些并发症，在小鼠模型中研究了哮喘相关表型的遗传调控。我们在A/J、AKR/J、BALB/cJ、C3 H/HeJ和C57 BL/6 J近交系以及（C3 H/HeJ x A/J）F1小鼠中，通过变应原暴露方案，描述了哮喘相关表型气道高反应性（AHR）、肺嗜酸性粒细胞和卵清蛋白（OVA）特异性血清免疫球蛋白（IG）E的菌株分布模式。AHR的表达在菌株之间不同，有时与肺嗜酸性粒细胞或血清IgE不一致。此外，我们确定了两个不同的数量性状位点（QTL）的过敏原诱导的AHR，Abhr 1（过敏原诱导的支气管高反应性）（lod = 4.2）和Abhr 2（lod = 3.7），在染色体2上的回交后代从A/J和C3 H/HeJ小鼠的易感性。此外，第7染色体上的QTL暗示与该性状连锁。这些QTL不同于我们以前发现的控制非炎性AHR在相同的十字架。阐明这些QTL背后的基因将有助于确定哮喘动物模型中调节AHR的生化途径，并可能为人类疾病的发病机制提供见解。
Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characterized the strain distribution patterns for the asthma-related phenotypes airway hyperresponsiveness (AHR), lung eosinophils, and ovalbumin (OVA)-specific serum immunoglobulin (Ig) E induced by allergen exposure protocols in A/J, AKR/J, BALB/cJ, C3H/HeJ, and C57BL/6J inbred strains and in (C3H/HeJ x A/J)F1 mice. Expression of AHR differed between strains and was sometimes discordant with lung eosinophils or serum IgE. Furthermore, we identified two distinct quantitative trait loci (QTL) for susceptibility to allergen-induced AHR, Abhr1 (allergen-induced bronchial hyperresponsiveness) (lod = 4.2) and Abhr2 (lod = 3.7), on chromosome 2 in backcross progeny from A/J and C3H/HeJ mice. In addition, a QTL on chromosome 7 was suggestive of linkage to this trait. These QTL differ from those we have previously found to control noninflammatory AHR in the same crosses. Elucidation of the genes underlying these QTL will facilitate the identification of biochemical pathways regulating AHR in animal models of asthma and may provide insights into the pathogenesis of human disease.