Genetic analysis of an asthma-related trait in mice

小鼠哮喘相关性状的遗传分析

• 批准号: 8197784
• 负责人: DAVID R. BEIER
• 金额: $ 45.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197784
• 关键词: AKR/J Mouse; Affect; Airway Resistance; Antigens; Asthma; Biochemical; Chromosome Mapping; Complex; Data; Development; Experimental Animal Model; Genetic; Haplotypes; Human; Inbred Strain; Individual; Investigation; Mediating; Methods; Molecular; Mus; Phenotype; Physiological; Population; Positioning Attribute; Quantitative Trait Loci; Resolution; Role; Stimulus; Testing; abstracting; airway hyperresponsiveness; antigen challenge; base; density; genetic analysis; mast cell; mutant; trait

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.

抽象的： 气道高反应性（AHR）是哮喘的关键生理组成部分。而啊 通过对抗原的敏化，可以在实验动物模型中诱导，并且可以通过抗原潜在 在敏感人类中的挑战，这也是非敏感（NA�）个体的证据。遗传 这个复杂特征的基础仍然难以捉摸。对证明可遗传na的老鼠的分析 气道高反应性提供了一种识别其基本分子基础的方法。我们有 先前使用的遗传映射来识别会议AHR的定量性状位置（QTL）。我们也有 使用遗传和药物分析来证明该性状是由肥大细胞介导的。 这项建议，我们计划继续对可遗传的基因座进行调查，使AHR易于使用 最先进的遗传策略，并评估肥大细胞在菌株特异性会议中的作用 啊，特质。