Genetically Modified Mouse Core

转基因小鼠核心

基本信息

批准号：
9983077
负责人：
DOUGLAS J EPSTEIN
金额：
$ 16.39万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9983077
关键词：
Address American Animals Bacterial Artificial Chromosomes Biological Models Biopsy CRISPR/Cas technology Collaborations Color Complement Cost efficiency Cryopreservation DNA Data Derivation procedure Development Digestive System Disorders Disease ES Cell Line Embryo Embryo Transfer Equipment Female Fertility Fertilization Fertilization in Vitro Fostering Freezing Gastrointestinal tract structure Gene-Modified Generations Genetic Genotype Goals Housing Implant In Vitro Incidence Individual Infection Injections Institution International Investigation Knock-in Laboratories Lasers Liver Liver diseases Messenger RNA Methods Microinjections Modeling Modification Molecular Monitor Mothers Mouse Strains Mus Mutation Operative Surgical Procedures Pancreas Pancreatic Diseases Pathogenicity Pathologic Pathway interactions Pennsylvania Physiological Population Productivity Protocols documentation Quality Control Reproducibility Research Research Personnel Resource Sharing Resources Secure Services Shipping Site Sum System Tail Techniques Technology Therapeutic Time Transgenes Transgenic Mice Transgenic Organisms Universities Uterus Vendor Work YAC Clone blastocyst cost cost effective cost efficient embryo cell embryo cryopreservation embryo quality embryonic stem cell endonuclease experience experimental study flexibility homologous recombination implantation insertion/deletion mutation mouse genome mouse model offspring pathogen pregnant pup research and development sperm cell sperm cryopreservation success targeted nucleases transcription activator-like effector nucleases

项目摘要

PROJECT SUMMARY (GENETICALLY MODIFIED MOUSE CORE) The significant incidence of digestive, liver and pancreatic diseases in the American population demands continued exploration of a broad array of corresponding mechanistic pathways, pathophysiologic sequelae, and potential therapeutic approaches. In many cases these investigations can only be accomplished, or can be accomplished most efficiently and relevantly, using model systems established in intact animals. The use of mouse models in these pursuits is now well established for their power, feasibility, flexibility, and enormous potential. Creation of such models, by targeted alterations of the mouse genome, is an essential component of an overall research effort in understanding normal functions and pathologic perturbations in the digestive tract, liver, and pancreas. The Genetically Modified Mouse Core (GMMC) provides investigators of the University of Pennsylvania Center for the Molecular Study of Digestive and Liver Diseases (CMSDLD) with the ability to carry out these technologically-demanding studies in a cost effective and efficient manner and enhance the rigor and relevance of these approaches. The GMMC has a dedicated and highly skilled staff that applies state-of-the-art equipment and techniques, and the facility consists of a microinjection suite, an adjacent dedicated cage room, and an off-site and highly secure cryopreservation storage facility. Major services available to CMSDLD investigators include the generation of transgenic mice by DNA pronuclear injection, creation of chimeric mice by ES cell injection into blastocysts, and direct genome mutation, editing, and modification via the use of targeted endonuclease (TALEN and Crispr-CAS technologies); these are complemented by the genotyping of founder mice, assisted (in vitro) fertilization, cryopreservation, long-term cryostorage, and shipping of frozen embryos or sperm to/from other facilities. To provide these services, the GMMC utilizes multiple microinjection platforms, laser-assisted technologies, state-of-the-art cryopreservation approaches, and highly efficient line re-derivation pipelines. All functions, from ordering services, to following workflow, to storing and sending out lines, are on-line and can be monitored in real-time. These efforts by the GMMC contribute substantially to the overall productivity of CMSDLD investigators and enhance the rigor and relevance of their studies to the mechanisms of digestive, liver, and pancreatic diseases in physiologically- intact mammalian systems. Moreover, the GMMC enhances interactions and collaborations for CMSDLD investigators and lowers the technical and financial barriers that would otherwise impede the application of these approaches for individual investigators. Thus the Genetically Modified Mouse Core contributes greatly to the research efforts of the CMSDLD.

项目摘要（转基因鼠标核心）美国人口消化系统、肝脏和胰腺疾病的高发病率要求继续探索一系列相应的机制途径、病理生理学后遗症、和潜在的治疗方法。在许多情况下，这些调查只能完成，或者只能使用在完整动物中建立的模型系统可以最有效和相关地完成。用途小鼠模型在这些领域的应用现已因其强大的功能、可行性、灵活性和巨大的应用而得到广泛应用。潜在的。通过有针对性地改变小鼠基因组来创建此类模型是了解消化道正常功能和病理扰动的整体研究工作，肝脏和胰腺。转基因小鼠核心（GMMC）为美国大学的研究人员提供了宾夕法尼亚消化和肝脏疾病分子研究中心 (CMSDLD) 有能力以具有成本效益和高效的方式开展这些技术要求高的研究，并增强这些方法的严谨性和相关性。 GMMC 拥有一支敬业且技术精湛的员工队伍，该设施拥有最先进的设备和技术，包括显微注射套件、相邻的专用笼室，以及场外高度安全的冷冻储存设施。主要服务 CMSDLD 研究人员可用的方法包括通过 DNA 原核注射产生转基因小鼠，通过将 ES 细胞注射到囊胚中，并直接进行基因组突变、编辑和合成来创建嵌合小鼠通过使用靶向核酸内切酶（TALEN 和 Crispr-CAS 技术）进行修饰；这些都是辅以创始人小鼠的基因分型、辅助（体外）受精、冷冻保存、长期冷冻保存以及将冷冻胚胎或精子运送到其他设施或从其他设施运送。为了提供这些服务， GMMC 利用多个显微注射平台、激光辅助技术、最先进的冷冻保存方法和高效的线路重新派生管道。所有功能，从订购服务到关注从存储和发送线路的工作流程都是在线的，并且可以实时监控。这些努力由 GMMC 极大地提高了 CMSDLD 研究人员的整体生产力，并提高了严谨性和他们的研究与消化、肝脏和胰腺疾病的生理机制的相关性完整的哺乳动物系统。此外，GMMC 加强了 CMSDLD 的互动与合作调查人员并降低技术和财务障碍，否则会阻碍应用这些方法适用于个别研究者。因此，转基因小鼠核心对 CMSDLD 的研究工作。