TRANSGENIC AND TARGETING SHARED RESOURCE PROJECT SUMMARY/ABSTRACT The Transgenic and Targeting Shared Resource (Transgenic SR) is an essential asset to Case Comprehensive Cancer Center (Case CCC) members' research, illustrated by the breadth of scientific program involvement and reflected in the large number of investigators who use this SR. Last year alone, 45 investigators, 40% of whom were Case CCC members, accounting for 39% of total usage, from 5 out of 7 of the Center’s programs used the SR. The Transgenic SR makes transgenic, chimeric, knockout, and knock-in mice and provides services in rederivation, cryopreservation, reanimation, in vitro fertilization and surgery. Central to the success of investigators with new mouse genetic models is the role this facility plays in consultation, education and training, as well as support after service. The Specific Aims of the Transgenic SR are to: 1. Provide Case CCC members with consultation, education and training. The Director of the Transgenic SR consults with Cancer Center members and their research staff to ensure they utilize the best technology to meet their experimental goals. The rapid evolution of CRISPR/Cas9 technologies makes consultation particularly important. 2. Provide Case CCC members with new mouse genetic models. The Transgenic SR generates the genetic variants of mice in a timely and cost-effective manner. 3. Provide Case CCC members with follow-up support through direct interaction and through the wealth of information available on the facility website. At last review, the Transgenic SR was rated Outstanding Merit. Throughout the current funding cycle (2012- 2016), the Transgenic SR provided services to 133 registered users, 41 (31%) of whom are Case CCC members, representing 5 of the Center’s 7 Programs. The Transgenic SR has had great success in gene targeting using CRISPR/Cas9. Since 2014, the SR has successfully completed over 30 new gene-targeted mutations in mice using this approach, the vast majority of which have been disease-causing missense mutations. The Transgenic SR is in the vanguard of transgenic cores in applying CRISPR/Cas9 technology. In the last funding period, the Transgenic SR assisted Case CCC members in: generating mice that model human mutations leading to cancer; identifying cancer susceptibility loci; generating mice for in vivo imaging of tumors; and investigating the basic biology of genes implicated in cancer. This SR is the only transgenic core in the Cleveland area, and it serves investigators throughout the region. As a consequence, it is strongly supported by CWRU. All Case CCC members have access to this jointly managed SR.