The programmatic goals of this application make a centralized Animal Core essential. This Core will enable the study of the innate immune response to infection in relevant murine models that reflect the infectious process as well as the local and systemic inflammation accompanying sepsis. Models of infection (cecal ligation puncture or peritonitis) and challenge with purified bacterial components (LPS, bacterial lipoproteins, etc.) will be established so that tissues and fluids can be obtained to characterize temporal changes in gene and protein expression during the infectious and inflammatory processes. Materials will be supplied to appropriate cores (Genomic, Proteomic, etc.) and in addition the Animal Core will implement novel high-throughput technologies (i.e., multiplexed cytokine measurements with the Luminex technology). In its totality the output of this core will provide a database to broaden our understanding of the molecular events associated with disease progression. Moreover use of novel, non-invasive imaging approaches (Xenogen technology) will provide new insights into how the innate immune system controls the infectious process. Animal model studies will include mouse strains with specific gene deletions (i.e., TLR2 -/-, MyD88 -/-, etc.) already in hand as well as novel strains bearing defects in innate immunity produced through the efforts of the Forward Genetics Core. This core, though its production of a conditional knockouts, will allow investigations of novel genes identified through the collective efforts of the investigators that comprise this program. Importantly, over time this Core will also be a major distributions source of conditional knockouts bred on appropriate backgrounds through the speed congenic program. In its totality the Animal Model Core represents a central and essential component of the overall program. It also represents a hitherto non-existent resource for the entire research community by providing a database characterizing in vivo models in normal as well as in novel strains of mice bearing conditional knockouts or single-gene mutations.
Showing the most recent 10 out of 46 publications
