The Mouse Core plays a central role in this proposal, providing for the breeding and management of the large colony of transgenic and knockout mice that will be generated for this project. Five different knockout strains have been or will be created for this project, and these will be each intercrossed with one another, as well as with 3-4 different strains of transgenic lines (tetO-responder lines), to generate multiple substrains. These animals are the source for all of the behavioral, physiological, pharmacological, anatomical and cell-based studies in the Program Project, and are a primary shared resource for all of the collaborative experiments among the three participating laboratories. The need for this core is justified by the large numbers of genetically modified mice that must be generated and maintained solely for the purposes of this project (see Budget Justification). The behavioral phenotyping experiments in particular require large numbers of animals of each strain and genotype, because the greater inherent variability of such experiments requires large numbers of animals to achieve statistical significance. The Mouse Core will leverage the infrastructure, personnel, equipment and other resources available in the Transgenic Animal Facility at Caltech (TAFCIT), while providing exclusive support for the generation, maintenance, breeding and shipping of transgenic and knockout mice strains associated with this Program Project.