Genetics of Host Resistance to Franciscella tularensis in Mice

描述(由申请人提供)：了解宿主对土拉方杆菌的抗性和敏感性的遗传学可以为病原体与其宿主之间的相互作用提供重要线索。它们可以揭示与致病相关的关键分子，例如病原体使用的受体，以及病原体对其高度敏感的宿主防御机制。它可以发现先天免疫系统和后天免疫系统的重要组成部分。我们将对来自抗病C57BL/6J和感病A/J、抗病BALB/CJ和感病A/J的F2群体进行基因组扫描，以确定QTL连锁。我们将利用细菌载量最低的F2后代与感病亲本进行回交。这允许相关基因的丰富，同时重组允许更紧密的定位。该项目将确定在宿主抵抗细菌感染的能力中至关重要的基因和途径。它专注于对引起兔热的细菌--图拉方济杆菌的抗药性。了解相关基因将导致更好的治疗方法和更好的疫苗。

DESCRIPTION (provided by applicant): Understanding the genetics of host resistance and susceptibility to Franciscella tularensis can provide important clues into the interaction between pathogens and their hosts. They can reveal critical molecules involved in both pathogenesis e.g. receptors used by pathogens, and host defense mechanisms to which the pathogen is exquisitely sensitive. It can uncover important components of both the innate and acquired immune system. We will perform a Genome Scan of F2 populations derived from resistant C57Bl/6J and susceptible A/J, and resistant BALB/cJ and susceptible A/J. To confirm QTL linkage we will perform backcross selection using FT resistance for selection. We will perform a backcross to the susceptible parent using F2 progeny that have the lowest bacterial load. This allows an enrichment of the relevant genes at the same time as recombination allows closer localization. This project will identify genes, and pathways that are critical in the ability of hosts to fight off bacterial infections. It concentrates on the resistance to the bacteria that causes rabbit fever, Franciscella tularensis. Understanding the genes involved will lead to better treatments, and better vaccines.