Genetics of Host Resistance to Franciscella tularensis in Mice

描述（申请人提供）：了解宿主对土拉弗朗西斯菌的抗性和易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。它们可以揭示致病机制中涉及的关键分子，例如病原体使用的受体，以及病原体对其非常敏感的宿主防御机制。它可以揭示先天性和获得性免疫系统的重要组成部分。我们将对来自抗性C57 B1/6 J和敏感A/J以及抗性BALB/cJ和敏感A/J的F2群体进行基因组扫描。为了确认QTL连锁，我们将使用FT抗性进行回交选择。我们将使用具有最低细菌负荷的F2后代与易感亲本进行回交。这允许相关基因的富集，同时重组允许更紧密的定位。该项目将确定基因和途径，这些基因和途径对宿主抵抗细菌感染的能力至关重要。它集中于对引起兔热的细菌的抵抗力，Franciscella tularensis。了解相关基因将有助于更好的治疗和疫苗。

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.