GENES CONTROLLING VIRUS INDUCED ASTHMA IN RATS

这项研究的长期目标是增加对 控制儿童易感性的基本遗传机制 病毒感染和过敏原暴露后的哮喘。这项研究 将使用病毒诱导和过敏原加重的哮喘的大鼠模型。 将研究遗传易感的BN大鼠和抗性的F344大鼠 继副流感病毒1型(仙台)病毒感染和 反复暴露卵清蛋白。具体目标是：1)评估 病毒感染与反复呼吸道变应原的相对作用 生命早期暴露对慢性呼吸道疾病发展的影响 特应性和非特应性哮喘的炎症和重塑及气道高反应性 非特应性大鼠(BN和F344)；2)确定遗传位点(定量 控制病毒诱导和致病的敏感性的性状基因座 过敏原加重的呼吸道炎症和哮喘样表型 利用全基因组扫描和连锁分析在(BN X F344)F1和 回交大鼠；3)培育具有染色体的同源大鼠品系 包含控制病毒易感性的基因座的片段 变应原诱导的哮喘样综合征的后续精细染色体 特异控制基因的定位研究与鉴定 哮喘样表型的发展。

The long-term goal of this research is to increase understanding of basic genetic mechanisms controlling susceptibility of children to asthma following viral infection and allergen exposure. The research will use a rat model of virus-induced and allergen-accentuated asthma. Genetically-susceptible BN rats and resistant F344 rats will be studied following parainfluenza virus type 1 (Sendai) virus infection and repeated ovalbumin exposure. The specific aims are: 1) To evaluate the relative contributions of viral infection and recurrent airway allergen exposure during early life on the development of chronic airway inflammation and remodeling and airway hyperresponsiveness in atopic and non-atopic rats (BN and F344); 2) To identify genetic loci (quantitative trait loci-QTLs) controlling susceptibility to virus-induced and allergen-accentuated airway inflammation and asthma-like phenotypes using genome-wide scan and linkage analysis in (BN X F344) F1 and backcross rats; and 3) To develop congenic rat strains with chromosomal segments containing loci that control susceptibility to virus and allergen-induced asthma-like syndrome for subsequent fine chromosomal mapping studies and identification of specific genes controlling development of asthma-like phenotype.