Animal Model Shared Resource

动物模型共享资源

基本信息

批准号：
10712890
负责人：
WINFRIED EDELMANN
金额：
$ 34.62万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-06-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10712890
关键词：
Ablation Accreditation Alleles Amino Acids Animal Husbandry Animal Model Biological Sciences Board Certification Breeding CRISPR interference CRISPR-mediated transcriptional activation CRISPR/Cas technology Cancer Center Support Grant Cancer Model Cancer cell line Caring Cells Clustered Regularly Interspaced Short Palindromic Repeats Constitution Constitutional Cryopreservation Derivation procedure Development Down-Regulation Embryo Ensure Enterobacteria phage P1 Cre recombinase Evaluation Fertilization in Vitro Gene Expression Gene Modified Gene Targeting Generations Genes Genotype Goals Hematologic Neoplasms Heterozygote Histologic Housing Human Injections Knock-in Mouse Knock-out Knockout Mice Label Maintenance Malignant Neoplasms Mammalian Cell Methodology Methods Microinjections Modification Mus Oocytes Pathologist Patients Principal Investigator Proteins RNA Reporter Genes Research Research Personnel Resource Sharing Rodent Services Solid Neoplasm Specificity Study models System Tamoxifen Techniques Technology Tissue Model Tissues Transgenes Transgenic Mice Transgenic Organisms Transplantation Xenograft procedure animal facility animal imaging base base editing conditional knockout cost cost efficient embryo cryopreservation embryonic stem cell genomic locus germ free condition human cancer mouse model human model imaging system implantation improved in vivo in vivo imaging in vivo imaging system inducible Cre innovation knock-down mouse genome mouse model neoplastic cell novel novel anticancer drug novel imaging technology offspring overexpression patient derived xenograft model preclinical study preservation programs red fluorescent protein reproductive sperm cryopreservation stem tumor tumor growth tumor xenograft

项目摘要

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

计划主任/首席研究员（最后，第一，中间）：楚，爱德华动物模型共享资源 - 项目摘要/摘要动物模型共享资源（AMSR）的目的是为人类癌小鼠模型的产生，外壳和分析。 AMSR为通过CRISPR/CAS9基因靶向技术以及常规的鼠标基因组修改小鼠基因组胚胎（ES）细胞中的基因靶向。 AMSR生成常规的敲除小鼠线，敲除在带有条件等位基因的小鼠线和小鼠线中，用于基因的时间和空间消融。 AMSR 还可以通过常规随机转基因为生成转基因鼠标线的服务提供服务通过将转基因的靶向插入到安全港基因组基因局中以确保稳定的基因表达。 AAALAC认可的AMSR动物设施提供特定的无病原体（SPF）啮齿动物外壳和宽阔畜牧服务的范围以及由董事会认证的兽医病理学家的服务。用于胚胎和精子冷冻保存和重新启动的综合鼠标生殖服务提供了转基因和基因靶向的鼠标线以及IVF服务。 AMSR建立了一个基因修改服务，为快速且经济高效的基因生成提供完整的服务修改了MECC研究者的小鼠线。此外，AMSR提供了强大的异种移植物通过系列移植的细胞植入和传播肿瘤移植物的方法学，并支持前关于鼠肿瘤中新型抗癌药以及人类患者衍生肿瘤异种移植物的临床研究（PDX）。最后，AMSR提供具有表达生物发光的肿瘤动物的体内IVI成像或荧光蛋白，允许对小鼠的肿瘤生长进行非侵入性定量。 AMSR有三个特定旨在实现这些目标：1）提供遗传产生所需的全面服务改良的人类癌症的小鼠模型和用于研究的异种移植小鼠模型血液学恶性肿瘤和患者衍生的实体瘤异种移植物； 2）为畜牧业提供服务保存转基因的小鼠系，包括精子和胚胎冷冻，以进行冷冻保存，重新保存转基因和基因靶向小鼠系的推导以及体外受精（IVF）服务； 3）提供支持MECC研究的创新方法和技术，包括新颖的CRISPR技术，例如基本编辑技术，CRISPR干扰（CRISPRI），CRISPR激活（CRISPRA）和CRISPR RNA 基因表达敲低的技术以及新型成像技术，以增加肿瘤细胞中可检测的荧光标签。 OMB No. 0925-0001/0002（修订版03/2020通过02/28/2023批准）页面