PROJECT SUMMARY – Transgenic and Chimeric Mouse Facility The Transgenic and Chimeric Mouse Facility (TCMF) at the Abramson Cancer Center (ACC) has been continuously funded by the NCI CCSG since 1989 under the guidance of Dr. Stephen Liebhaber, Professor of Genetics and Medicine. Dr. Liebhaber is an experienced investigator with considerable expertise in technologies and experimental approaches that center on transgenic technologies, developmental biology, and mammalian gene targeting. An experienced technical team, led by Dr. Jean Richa, provides expertise in a full range of transgenic technologies, enabling the TCMF to regularly introduce new and improved services. Among the services provided by the Transgenic and Chimeric Mouse Facility are generation of genetically altered mice via direct genome editing (CRISPR/Cas9, and less frequently Zn finger and TALEN technologies), by DNA microinjections into fertilized oocyte to create transgenic lines, or by generation of chimeric mice via embryonic stem cell injection into blastocysts. The Transgenic and Chimeric Mouse Facility also carries out embryo re-derivation, embryo and sperm cryopreservation, in vitro fertilization (IVF), and centralized cryopreservation storage. The TCMF uses state-of-the-art laser conditioning of the zona to facilitate IVF and has intracytoplasmic sperm injection capability on-line 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 TCMF services. ACC members accounted for 29 of 71 investigators (41%) using the Shared Resource during the most recent reporting period (07/01/18- 06/30/19). Additional Institutional (non-CCSG) support is provided for equipment maintenance and facility infrastructure upgrades and maintenance. In one example of the supported high-impact research, the TCMF generated a series of mouse cell lines, which were used to demonstrate opposing effects of the LIN28B-IMP1 axis on post-transcriptional regulation of canonical WNT signaling, with implications for intestinal homeostasis, regeneration and tumorigenesis (Chatterji et al., Genes Dev, 2018). The TCMF provides cutting edge technologies to generate transgenic mice needed for rigorous cancer research studies conducted by ACC members.