Core A: Mouse Genetics and Genomics (Core Leader: Ferris) Abstract Mouse models of human diseases, such as Mycobacterium tuberculosis (Mtb), have proven invaluable for understanding the underlying genetic, molecular and physiological or immunological basis of these disease processes. Recent work has shown that mouse models that incorporate population-wide genetic diversity can model unique aspects of the response to Mtb infection, as well as immunization against Mtb, with several of these strains recapitulating unique aspects of human disease. The mouse genetics core serves this larger program by identifying/confirming the genetic features driving these unique aspects of host responses to Mtb via experimental crosses and infection or immunization studies between mouse strains segregating candidate genome regions, concurrent with genomic and transcriptomic refinement of the candidate variants and pathways. Lastly, the core will incorporate the results of these analyses to generate improved models of Mtb disease via the generation of new congenic or mutant mouse strains for the research projects to dissect the impact of these models and genetically variable pathways on Mtb disease.