The ability to manipulate the mouse genome through transgenic and knock-out or knock-in technologies has revolutionized modern Immunology. The purpose of this core facility (Core B) is to integrate the transgenic and gene targeting approach into the studies of host-pathogen interaction, a major thrust of the program project "Mouse models for understanding host-pathogen interactions". This Transgenic/Knockout Mouse Core will provide the critical technical capability to generate and to maintain transgenic and mutant mice commonly used by two or more investigators of the program project (PPG). In particular, this Core will complement Core C to provide transgenic mice expressing fluorescent proteins to be used for imaging studies. Core B will also generate and distribute transgenic strains of mice as needed by the individual investigator in the PPG. In aim 1, C57Bl/6 transgenic mice expressing fluorescent genes, whose expression is driven by different promoter/enhancers will be generated and maintained for use in video imaging experiments. These include mice expressing membrane Cyan Fluorescent Protein (CFP) in dendritic cells or macrophages and mice with CFP or YFP (Yellow Fluorescent Protein) expressed in all cell types. In aim 2, knock-out/knock-in mice with genes involved in innate immunity will be maintained as well as back-crossed to C57BI/6 or Balb/c if necessary. These mice, including DC- and macrophage-specific FADD-/-, MyD88-/-, IFN-alpha/betaR-/-, TRAIL-R-/-, NK deficient mice, NKG2D-/-, IL-12/GFP (Green Fluorescent Protein) knock-in and lFN-gamma/GFP knock-in mice, will be provided to investigators in the PPG for their biochemical, infection or imaging experiments. In aim 3, Core B will generate and provide transgenic mice for the specific needs of the individual PPG investigator. Completion of these aims is necessary and essential for the success of the PPG designed to understand how the immune system interacts with model pathogens.