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Host Genes and Resistance/Sensitivity to Military Priority Pathogens

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Annual rept. 1 Jun 2010-31 May 2011

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The major objective of the award is to identify host genetic locipathways whose expressionlack of expression correlate with resistance vs. susceptibility to pathogenic challenge using recombinant inbred BXD mice. The pathogens studied are Francisella tularensis FT, Burhholderia pseudomallei Bp, Acinetobacter baumannii Ab, Leishmania major Lm, SARS, H5N1 avian influenza. A new FT reporter plasmid has been constructed resulting in bioluminescence production, which could be used to follow FT growth in vitro and in vivo. Preliminary observations on differential susceptibility to Bp 1026-mediated disease in BXD mouse strains have identified two suggestive QTLs, encoded on Chr 4 and 7. We are also carrying out parallel studies to identify cellular pathways responsible for genetic susceptibility to Bp infection using mice deficient in the inflammasome. We have identified 33 potentially useful phenotypic differences between B6 and D2 mice infected with Acinetobacter, and a QTL on Chr10 that may correlate with immune responsiveness. The Influenza project has identified a significant QTL associated with early production of proinflammatory cytokines on Chr 6. The Lm project has identified 2 suggestive loci regulating parasite burden. The mouse genomics core is continuing to develop new BXD strains. The bioinformatics core has begun analysis of data obtained from BXD mouse strains infected with Acinetobacter.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Biology
  • Medicine and Medical Research
  • Microbiology

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