Genetics of Host Resistance to Franciscella tularensis in Mice

小鼠对土拉弗朗西斯氏菌宿主抗性的遗传学

• 批准号: 7259227
• 负责人: JEFFREY Allen FRELINGER
• 金额: $ 21.9万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7259227
• 关键词: A/J Mouse; Architecture; BALB/cJ Mouse; Backcrossings; Bacterial Infections; Blood; Candidate Disease Gene; Chromosome Mapping; Collaborations; Consomic Strain; Critical Pathways; Data; Evolution; Fever; Francisella tularensis; Generations; Genes; Genetic; Genetic Recombination; Genome Scan; Genomics; Haplotypes; Host Defense; Host Defense Mechanism; Host resistance; Immune system; Immunologics; Immunology; Individual; Infection; Laboratories; Lead; Liver; Lung; Maps; Mouse Strains; Mus; Organ; Oryctolagus cuniculus; Parents; Pathogenesis; Phenotype; Physiological; Population; Predisposition; Process; Quantitative Genetics; Quantitative Trait Loci; Resistance; Spleen; Time; Vaccines; bacterial resistance; congenic; day; experience; fighting; insight; interest; pathogen; receptor; research study; trait

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.

描述（由申请人提供）：了解宿主抵抗力和对方济各会的易感性的遗传学可以为病原体及其宿主之间的相互作用提供重要的线索。他们可以揭示涉及这两种发病机理的关键分子，例如病原体使用的受体和病原体非常敏感的宿主防御机制。它可以发现先天和获得的免疫系统的重要组成部分。我们将对源自抗性C57BL/6J和易感A/J的F2种群进行基因组扫描，以及耐药的BALB/CJ和易感A/J。为了确认QTL链接，我们将使用FT电阻进行选择进行反向交叉选择。我们将使用具有最低细菌载荷的F2后代对易感母体进行反向交叉。这允许同时富集相关基因，因为重组允许更紧密的定位。该项目将确定基因和宿主抵抗细菌感染能力至关重要的途径。它集中于引起兔子热的细菌的抗性，即方济各会。了解所涉及的基因将导致更好的治疗方法和更好的疫苗。