Core B (Animal Component) - Project Summary All research projects of this Program Project (PP) will rely on the use of genetically engineered mouse (GEM) models to investigate the roles and mechanism of Nuclear Receptors, transcription factors and their coregulators in energy and metabolic homeostasis and disease. More specifically, at least 34 GEM mouse lines will be used, and thousands of male and female mice will be produced by breeding in house during the funding period of this PP. Therefore, this Animal Component of Core B is essential for the success of this PP by integrating expensive equipment, advanced technology, experienced personnel and animal resources. As shown by preliminary studies, Core B has generated/established multiple GEM lines and developed CRISPR-Cas9-mediated mouse gene editing systems. Core B is dedicated to achieving 3 major objectives. Firstly, Core B will use its specialized expertise, state-of-the-art equipment and adequate facilities to generate GEM lines for all investigators of this PP. Core B has established the necessary methods to edit the mouse genome by homologous recombination- based gene targeting in ES cells or CRISPR/Cas9-based gene editing in 1-cell mouse embryos. Core B will generate all GEM lines needed by the investigators of this PP. Secondly, Core B will provide high quality mouse services to manage GEM line colonies and produce genotype-defined and age/sex-matched mice for all investigators of this PP. Specifically, Core B will breed and maintain all of the 34 mouse lines used by this PP. Core B will use our colony expansion protocol to produce large numbers of genotype/age/sex-matched mice for experimental analysis. Core B also will perform genotype analysis, super ovulation, embryo and sperm cryopreservation, and in vitro fertilization services to help the investigators of this PP for managing their mouse colonies, preserving GEM lines, transferring mouse lines between institutes, and saving animal husbandry expenses. Finally, Core B will integrate the efficient usage of animal resources by all investigators of this PP. Because of the large-scale operation of mouse models and the sharing features of multiple mouse lines among the projects of this PP, centralized integration of equipment, expertise and valuable mouse resource will be essential for both scientific success and cost effectiveness. Core B will minimize the expenses of animal experiments by consolidating the usage and management of equipment, expertise, animal facility, mouse maintenance and production. In addition, Core B will serve as a resource for execution and technical training in the use of all animal manipulations needed and oversee the care and use of experimental mice for this PP.