Transgenic Mouse Genome Editing Core

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PROJECT SUMMARY (Transgenic Mouse Genome Editing Core) The Transgenic Mouse Genome Editing Core (TMGEC) has been an integral part of the Diabetes Research Center (DRC) at the Perelman School of Medicine, University of Pennsylvania since 1997. The TMGEC is directed by Dr. Douglas Epstein, PhD, Professor and Vice Chair, Department of Genetics. Dr. Epstein is an experienced investigator with considerable expertise in technologies and experimental approaches that center on mouse models of disease, developmental genetics, and genome editing. An experienced technical team, led by Dr. Jean Richa, provides expertise in a full range of transgenic technologies, enabling the TMGEC to regularly introduce new and improved services. Services provided by the TMGEC include the generation of genetically altered mice by direct genome editing (CRISPR/Cas9), DNA microinjection into fertilized oocytes to create transgenic lines, the generation of chimeric mice via embryonic stem cell injection into blastocysts. The TMGEC also carries out embryo re-derivation, embryo and sperm cryopreservation, in vitro fertilization (IVF), and centralized cryopreservation storage. The TMGEC uses state-of-the-art laser conditioning of the zona to facilitate IVF and has intracytoplasmic sperm injection capability to complement IVF services. Newly developed services during the current funding period include the major expansion of cryopreservation services with corresponding expansion of the cryopreservation facility, integration of CRISPR/Cas9 direct genome modifications with a newly established Perelman School of Medicine CRISPR core, and electroporation of DNA and RNA into embryos to increase throughput and decrease wait time for TMGEC services. In the past 5 years, 48 DRC investigators used TMGEC services to generate 225 independent mouse lines (primarily by CRISPR/Cas9 editing) and to store 134 mouse lines (by cryopreservation). Usage is expected to stay the same, or increase over the next five years. Additional Institutional (non-DRC) support is provided for equipment maintenance and facility infrastructure upgrades and maintenance. An extensive network of collaborations exist within the DRC focusing on the use of genetically modified mouse models of diabetes, obesity and metabolic disorders. These joint projects among DRC investigators highlight the role of the TMGEC not only as an essential technical resource but also as a key hub for collaborative research among DRC investigators, as exemplified by the numerous joint publications and successful grant applications arising from mice generated, stored, and/or re-derived by the TMGEC.