Genetic Models

项目总结/摘要 由拟议的肌肉骨骼疾病研究中心支持的每个项目负责人 （CMDR）将需要产生新的转基因小鼠或细胞系，以实现其目标， 建议的研究。为了满足COBRE的需求，将通过扩展 现有的转基因小鼠设施在阿肯色州医学科学大学（UAMS）。该现有 该设施在生产转基因小鼠方面有着良好的记录。然而，为了满足拟议的CMDR的需要， 将有必要通过增加新的技术和人员来扩大其能力。这将是完成 部分使用最近开发的基于CRISPR-Cas9系统的工具来提供基因编辑 在小鼠和细胞系中提供服务。这种服务的扩展将创建一个遗传模型核心，此外， 为满足COBRE项目负责人的需求，将为研究提供新的尖端服务。 社区在UAMS，其附属机构，并在整个阿肯色州。在具体目标1中，我们建议提供 为转基因小鼠的生产和维护提供最先进的服务。一代服务 将包括通过原核注射设计和创造转基因和基因靶向小鼠。维护 服务项目包括精子冷冻保存，体外受精和品系再衍生。在具体目标2中， 建议开发支持遗传模型创建和使用的新方法和服务。新服务 将开发CMDR成员所需的技术，如创建转基因细胞系。此外，本发明还提供了一种方法， 核心人员将通过评估，不断更新用于细胞和小鼠修饰的基因编辑工具， 目前的文献和出席讲习班和会议。在具体目标3中，我们建议提供培训 以及与使用遗传模型有关的教育。项目负责人和其他用户将接受培训， 并准确地产生实验性的转基因小鼠队列，我们将教育用户的潜力， 这是使用这些模型时经常遇到的问题。核心人员也将教育研究 社区在UAMS和其他校园在阿肯色州，有关的服务和技术，可通过 基因模型核心拟议的CMDR的科学主题是， 有一个分子基础，其鉴定将指导开发特异性和有效的 治疗遗传模型核心与这一主题是一致的，因为它将允许项目领导者快速 并有效地测试特定分子变化在影响骨骼的病理过程中的作用， 其中骨骼起主要作用，如骨髓瘤或乳腺癌转移。

PROJECT SUMMARY/ABSTRACT Each of the Project Leaders supported by the proposed Center for Musculoskeletal Disease Research (CMDR) will require the generation of new genetically modified mice or cell lines to accomplish the goals of their proposed studies. To serve the needs of this COBRE, a Genetic Models Core will be created by expanding an existing transgenic mouse facility at the University of Arkansas for Medical Sciences (UAMS). This existing facility has a strong record of producing transgenic mice. However, to meet the needs of the proposed CMDR, it will be necessary to expand its capabilities by adding new technologies and personnel. This will be accomplished in part using recently developed tools that are based on the CRISPR-Cas9 system to provide gene-editing services in both mice and cell lines. This expansion of services will create a Genetic Models Core that, in addition to meeting the needs of the COBRE Project Leaders, will provide new cutting-edge services to the research communities at UAMS, its affiliated institutions, and across Arkansas. In Specific Aim 1, we propose to provide state-of-the-art services for the generation and maintenance of genetically modified mice. Generation services will include the design and creation of transgenic and gene-targeted mice by pronuclear injection. Maintenance services will include sperm cryopreservation, in vitro fertilization, and strain rederivation. In Specific Aim 2, we propose to develop new approaches and services that support genetic model creation and use. New services needed by CMDR members, such as creation of genetically modified cell lines, will be developed. In addition, Core personnel will continuously update gene-editing tools for cell and mouse modification via evaluation of current literature and attendance at workshops and meetings. In Specific Aim 3, we propose to provide training and education related to the use of genetic models. Project Leaders and other users will be trained to efficiently and accurately produce experimental cohorts of genetically modified mice, and we will educate users on potential problems that are often encountered with the use of such models. Core personnel will also educate the research communities at UAMS and other campuses in Arkansas, about the services and technologies available through the Genetic Models Core. The scientific theme of the proposed CMDR is that conditions that lead to deterioration of the skeleton have a molecular basis whose identification will guide development of specific and effective therapies. The Genetic Models Core is consistent with this theme in that it will allow Project Leaders to rapidly and efficiently test the role of specific molecular changes in pathological processes the affect the skeleton or in which the skeleton plays a major role, such as myeloma or breast cancer metastases.