PROJECT SUMMARY MOUSE RESOURCES AND VALIDATION CORE (CORE C) The Mouse Resources and Validation Core (MRVC, Core C) for The Center for Systems Neurogenetics of Addiction will serve several interrelated functions. The first will be to provide cohorts of mice for neurobehavioral screening and biobanking. To accomplish this, the Core will provide expert management of the breeding capacity for cohorts of Collaborative Cross strains and will also manage the acquisition and movement of Diversity Outbred (DO) and founder inbred strains from the JAX Repository to the CSNA. The Core will also provide capacity for variant validation through the creation of novel variants in mouse iPS/ES cells, in vitro screening of the engineered cell lines for functional testing and, for a subset of promising functional variants, capacity for in vivo validation through CRISPR/Cas9 technology. The Core will provide expertise and infrastructure to create new mouse models for gene variants, which will be archived at JAX and will be made available for distribution to the global research community according to NIH sharing policy and our resource sharing plan. Finally, the Core will conduct primary research on exciting new tools and technologies for cloning DO mice with the ultimate goal of developing best practices for functional validation of extreme, highly polygenetic phenotypes found in the DO genomes. This latter activity will deliver an unprecedented type of retrievable, but genetically complex addiction models for functional studies and further genetic and genomic characterization.