Abstract Mouse models provide highly tractable models with which to assess, identify and mechanistically characterize the role of genetic variants on infectious disease responses. The Mouse Genetics Core has been at the forefront of designing experimental crosses, sequence datasets and other mouse resources with which to investigate and perturb polymorphic immune networks. Following the identification of polymorphic host genome regions, aberrant mouse lines, and discordant immune spreads or candidate genes and pathways from human studies (in close collaboration with the Projects and the Systems Genetics and Bioinformatics core), we will generate a variety of mouse experimental models for the Projects to further assess, identify and characterize these processes. These models will include F1 panels contrasting variant disease alleles, F2 mapping populations, and mouse strains with modified candidate genes. Concurrently, designing the appropriate experiments for the study of viral disease requires an understanding of the underlying immune composition of individuals. Therefore, the Core will identify and further characterize genetic variants impacting basal immune responses; both intra-cellular as well as at the whole-organism level. These data will be provided to the projects to enhance their assessment of antiviral and/or perturbed response.