Host Genes and Resistance/Sensitivity to Military Priority Pathogens

Abstract

The major objective of the award is to identify host genetic loci/pathways whose expression/lack 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.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2011
Accession Number
ADA624226

Entities

People

  • Gerald I. Byrne

Organizations

  • University of Tennessee

Tags

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Bacteria
  • Bayesian Networks
  • Body Weight
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Data Analysis
  • Genetics
  • Health Services
  • Infectious Diseases
  • Lymphatic System
  • Lymphocytes
  • Medical Personnel
  • Microbiology
  • Sars
  • Viruses

Fields of Study

  • Biology

Readers

  • Infectious Disease/Epidemiology
  • Microbial Pathology
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech