Genome Editing and Animal Models

PROJECT SUMMARY / ABSTRACT Genetically engineered animals and cell lines are widely used as models to define the mechanisms underlying cancer etiology and progression and to evaluate strategies for cancer treatment and prevention. The Genome Editing and Animal Models Shared Resource (GEAM) has served as a shared resource for the University of Wisconsin Carbone Cancer Center (UWCCC) for over three decades and is one of the elite facilities in the United States to offer the comprehensive services required to generate, characterize, and preserve genome edited animal models. GEAM’s mission is to make state-of-the-art genome editing technologies for animals and cell lines as well as cryopreservation services accessible to UWCCC members. Specific Aim 1 is to generate novel, highly relevant, genome edited or transgenic animal models of human cancers. GEAM staff serve UWCCC members in all aspects of experiment planning, including the design of efficient approaches to achieve the desired genome manipulation using CRISPR, homologous recombination, and transgene-based approaches; the identification of animals that carry the desired genome edit or transgene; and the minimization of off target edits. Our extensive experience in reproductive biology, embryo manipulation, and animal husbandry enable GEAM to edit the genomes of mouse and rat strains that exhibit low reproductive capacity. Specific Aim 2 is to develop clonally derived, genome edited, cell lines for use in cancer research. In the current cycle, GEAM established a pipeline that is capable of editing the genome of a wide variety of established cell lines and implemented a state-of-the-art automated clone tracking system. Specific Aim 3 is to provide state-of-the-art reproductive biology services that enable animal model banking, recovery, and sharing. GEAM’s sperm and embryo cryopreservation capabilities reduce animal husbandry costs and allow recovery of cancer models through embryo transfer or in vitro fertilization. Rederivation of rodent models eliminates pathogens that may compromise research or prevent animal model importation into campus vivaria or sharing between collaborators. In the current cycle, GEAM has continued to modernize our infrastructure through purchases of new equipment using institutional support, adopted the latest and most advanced genome editing methods, and added highly trained staff to best meet the increasing and technically challenging needs of our users. Thirty-nine unique UWCCC program members were served by GEAM during the current Cancer Center Support Grant (CCSG) funding cycle. Support from the CCSG enables GEAM’s services to be tailored to the unique needs of UWCCC members and provided at costs below those of commercial vendors or similar cores at other research universities. GEAM’s first rate, cost effective, services enhance the ability of UWCCC investigators to conduct innovative research and advance the strategic mission of the Center. Data from biennial surveys of UWCCC members indicate GEAM’s services are high quality and critical to our members’ research.