Genetic analysis of an asthma-related trait in mice

摘要： 气道高反应性(AHR)是哮喘的重要生理成分。而AHR是 在实验动物模型中可通过对抗原致敏而诱导，并可被抗原增强 在致敏的人类中，这一挑战在未致敏的(自然)个体中也很明显。基因 这一复杂特征的基础仍然难以捉摸。对表现出可遗传幼稚的小鼠的分析 气道高反应性为确定其潜在的分子基础提供了一种手段。我们有 以前使用遗传作图来识别与AHR相关的数量性状基因座(QTL)。我们还有 使用遗传和药理学分析证明这一特性是由肥大细胞介导的。在……里面 在这项建议中，我们计划继续我们对易患AHR的可遗传基因座的调查 最先进的遗传策略，并评估肥大细胞在赋予菌株特异性的作用 AHR特征。

Abstract: Airway hyperresponsiveness (AHR) is a key physiological component of asthma. While AHR is inducible in experimental animal models by sensitization to antigen and can be potentiated by antigen challenge in sensitized humans, it is also evident in non-sensitized (na¿ve) individuals. The genetic basis of this complex trait has remained elusive. Analysis of mice that demonstrate heritable na¿ve airway hyperresponsiveness provides a means to identify its underlying molecular basis. We have previously used genetic mapping to identify quantitative trait loci (QTLs) that confer AHR. We have also used genetic and pharmacological analysis to demonstrate that this trait is mediated by mast cells. In this proposal, we plan to continue our investigation of the heritable loci that predispose to AHR using state-of-the-art genetic strategies, and to assess the role of mast cells in conferring the strain-specific AHR trait.