PROJECT SUMMARY/ABSTRACT – CORE B Project Leaders supported by the Center for Musculoskeletal Disease Research (CMDR) and other members of the Center will require the generation of new genetically modified mice to accomplish the goals of their proposed studies. The Genetic Models Core established at University of Arkansas for Medical Sciences (UAMS) during Phase 1 of this COBRE will serve these needs. This core was an outgrowth of an existing transgenic mouse core with a strong record of producing transgenic mice. Expansion of this facility during Phase 1, made possible by COBRE support, allowed the core to effectively serve Project Leaders, other members of the CMDR, and investigators at affiliated institutions and across Arkansas. For Phase 2, we propose to build on this success by maintaining the high-quality services provided by the Core and working to develop new services based on cutting-edge technologies. In Aim 1, we propose to maintain the Genetic Models Core for Project Leaders and other CMDR members by implementing a successful business plan to operate a facility dedicated to the generation, use, and maintenance of genetically modified mice. In Aim 2, we will provide genetic-model services to Project Leaders and other CMDR members. Generation services will include the design and creation of transgenic or gene-edited mice by pronuclear injection. Maintenance services will include sperm cryopreservation, in vitro fertilization, and strain rederivation. New approaches will be developed and existing approaches will be optimized in collaboration with Project Leaders and other CMDR members. Core personnel will continuously update gene-editing tools for mouse modification via evaluation of current literature and attendance at workshops and meetings. In Aim 3, we propose to continue to provide training and education related to the use of genetic models. Project Leaders and other users will be trained to efficiently and accurately produce experimental cohorts of genetically modified mice, and we will educate users on potential problems that are often encountered with the use of such models. Core personnel will also educate the research communities at UAMS and other campuses in Arkansas about the services and technologies available through the Genetic Models Core. The scientific theme of the CMDR is that identification of molecular contributors to musculoskeletal dysfunction and disease will guide development of effective therapies. The Genetic Models Core is consistent with this theme in that it will allow Project Leaders to rapidly and efficiently test the roles of specific molecular changes in pathological processes that affect the skeleton or in which the skeleton plays a major role.