Animal Model Shared Resource

Program Director/Principal Investigator (Last, First, Middle): Chu, Edward ANIMAL MODEL SHARED RESOURCE - PROJECT SUMMARY/ABSTRACT The objective of the Animal Model Shared Resource (AMSR) is to provide a comprehensive a service for the generation, housing, and analysis of mouse models of human cancer. The AMSR provides services for the modification of the mouse genome through CRISPR/Cas9 gene targeting technology as well as conventional gene targeting in embryonic stem (ES) cells. The AMSR generates conventional knockout mouse lines, knock- in mouse lines and mouse lines with conditional alleles for the temporal and spatial ablation of genes. The AMSR also provides services for the generation of transgenic mouse lines either by conventional random transgene integration, or by targeted insertion of transgenes into safe harbor genomic loci to ensure stable gene expression. An AAALAC-accredited AMSR animal facility provides specific pathogen-free (SPF) rodent housing and a broad spectrum of animal husbandry services, as well as the services of a board-certified veterinary pathologist. Comprehensive mouse reproductive services for embryo and sperm cryopreservation and re-derivation of transgenic and gene-targeted mouse lines as well as IVF services are offered. The AMSR established a Gene Modification Service to provide a complete service for the rapid and cost-efficient generation of genetically modified mouse lines to MECC investigators. Furthermore, the AMSR provides a robust array of xenograft methodologies for cell implantation and propagation of tumor grafts by serial transplantations, and supports pre- clinical studies on novel anticancer agents in murine tumors as well as in human patient-derived tumor xenografts (PDX). Finally, the AMSR provides in vivo IVIS imaging of animals bearing tumors that express bioluminescent or fluorescent proteins, allowing non-invasive quantitation of tumor growth in mice. The AMSR has three Specific Aims to accomplish these goals: 1) To provide comprehensive services required for the generation of genetically modified mouse models of human cancer and the generation of xenotransplantation mouse models for studying hematologic malignancies and patient-derived solid tumor xenografts; 2) To provide services for husbandry and preservation of genetically modified mouse lines including sperm and embryo freezing for cryopreservation, re- derivation of transgenic and gene-targeted mouse lines and in vitro fertilization (IVF) services; and 3) To provide innovative methods and technologies to support MECC research including novel CRISPR technologies such as base edit technology, CRISPR interference (CRISPRi), CRISPR activation (CRISPRa) and CRISPR RNA technology for knockdown of gene expression as well as novel imaging technologies to increase the range of detectable fluorescent labels in tumor cells. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page