GENETIC DISSECTION OF MYCOBACTERIAL INFECTION

分枝杆菌感染的基因解剖

• 批准号: 6795127
• 负责人: ERWIN SCHURR
• 金额: $ 30万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-14 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6795127
• 关键词: Mycobacterium bovis; Mycobacterium tuberculosis; alveolar macrophages; bacterial genetics; genetic markers; genetic strain; genetic susceptibility; host organism interaction; laboratory mouse; microarray technology; quantitative trait loci; tuberculosis

DESCRIPTION (provided by applicant) The objective of the studies proposed in this application is to identify genotypic combinations of mice and mycobacteria that result in significant alterations of host responses to experimental mycobacterial infection. Susceptibility or resistance to experimental infection will be defined by determination of median survival time, weight loss, mycobacterial load in the lung and spleen, and in addition various immunological parameters in lung and other tissues. In these experiments, the host genome will be varied by use of 37 recombinant congenic strains (RCS), which are derived from inbred progenitors that are either susceptible to tuberculosis (A/J, abbreviated A) or resistant to tuberculosis (C57BL/6J, abbreviated B). The AcB/BcA RCS are now fully inbred and genotyped with a dense set of genome-wide microsatellite markers. These strains will be infected with a panel of Mycobacterium tuberculosis and M. bovis strains that have been deleted for genome regions associated with attenuation of BCG vaccines. The infection protocol in the RCS will reveal informative, significant deviations from the "expected" or "parental" disease phenotypes which signify the presence of quantitative trait loci (QTL) with strong effect on phenotype expression and possibly specific gene(s) interaction between the host and pathogen. In RCS carrying QTL with strong effect on phenotype expression, changes in gene expression level in both lung macrophages and intracellular mycobacteria will be revealed by microarray analysis. The knowledge to what extent host responses in mycobacterial infections are a reflection of specific host pathogen combinations will be crucial for our understanding of the epidemiological flow of M. tuberculosis through an exposed population.

描述（由申请人提供） 本申请中提出的研究目的是确定 小鼠和分枝杆菌的基因型组合导致显著的 宿主对实验性分枝杆菌感染反应的改变。 对实验感染的敏感性或抗性将通过以下定义： 测定中位生存时间、体重减轻、 肺和脾，以及肺和 其他组织。 在这些实验中，宿主基因组将通过使用 37个重组同源菌株（RCS），来自近交系 对结核病易感的祖细胞（A/J，缩写为A） 或对结核病具有抗性（C57 BL/6 J，缩写为B）。 AcB/BcA RCS是 现在完全近交和基因分型与一组密集的全基因组微卫星 标记。 这些菌株将感染一组分枝杆菌 结核和M.基因组区域缺失的牛菌株 与卡介苗减毒有关。 感染协议在 RCS将揭示与“预期”或“预期”之间的信息性、重大偏差。 表示数量性状存在的“亲本”疾病表型 对表型表达有强烈影响的基因座（QTL）， 宿主和病原体之间的基因相互作用。 在携带QTL的RCS中， 对表型表达的强烈影响， 肺巨噬细胞和细胞内分枝杆菌都将通过 微阵列分析。 了解宿主在多大程度上 分枝杆菌感染是特定宿主病原体的反映 对于我们理解流行病学的流动， 分枝结核病通过暴露人群传播。