Genetically Modified Mouse Core

项目总结(转基因鼠芯) 消化、肝脏和胰腺疾病在美国人群中的显著发病率 继续探索一系列相应的机械途径、病理生理后遗症、 和潜在的治疗方法。在许多情况下，这些调查只能完成，或者可以完成 使用在完整动物身上建立的模型系统，以最有效和最相关的方式完成。它的用途 以其强大的、可行的、灵活的和巨大的 潜力。通过有针对性地改变小鼠基因组来创建这样的模型，是 一项全面的研究工作，旨在了解消化道的正常功能和病理变化， 肝脏和胰腺。转基因小鼠核心(GMMC)为加州大学的研究人员提供了 宾夕法尼亚州消化和肝病分子研究中心(CMSDLD)有能力 以符合成本效益和效率的方式进行这些对技术要求很高的研究，并加强 这些方法的严密性和相关性。GMMC拥有一支敬业的高技能员工队伍，适用于 最先进的设备和技术，该设施包括一个微量注射套件，一个相邻的 专用的笼屋，以及非现场高度安全的冷冻保存储存设施。主要服务 CMSDLD研究人员可以使用的方法包括通过DNA原核注射产生转基因小鼠， 通过将ES细胞注射到囊胚中创造嵌合小鼠，并直接基因组突变、编辑和 通过使用靶向内切酶进行修饰(TALEN和Crispr-CAS技术)；这些是 辅以方正小鼠的基因分型，辅助(体外)受精，冷冻保存，长期 冷冻储存，冷冻胚胎或精子往返于其他设施。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，以及高效的线路再衍生管道。所有功能，从订购服务到以下各项 存储和发送线路的工作流程都是在线的，可以实时监控。美国政府的这些努力 GMMC大大提高了CMSDLD调查人员的整体生产力，并增强了严谨和 他们的研究与消化、肝脏和胰腺疾病的生理学机制的相关性 完整的哺乳动物系统。此外，GMMC加强了CMSDLD的互动和合作 并降低了技术和财政障碍，否则将阻碍应用 这些方法是针对个别调查人员的。因此，转基因小鼠的核心对 CMSDLD的研究成果。

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.