Genetics of Host Resistance to Franciscella tularensis in Mice

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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.