Genetic Models

项目摘要/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来实现其目标 建议进行的研究。为了满足Cobre的需求，将通过扩展一个 阿肯色大学医学科学分校(UAMS)现有的转基因小鼠设施。这是现有的 该公司在生产转基因小鼠方面有着很好的记录。然而，为了满足拟议的Cmdr的需要，它 将有必要通过增加新的技术和人员来扩大其能力。这将会实现的 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 在小鼠和细胞系中都有服务。这种服务的扩展将创建一个遗传模型核心，此外 为了满足科布雷项目负责人的需求，将为研究提供新的尖端服务 UAMS、其附属机构以及整个阿肯色州的社区。在具体目标1中，我们建议提供 为培育和维护转基因小鼠提供最先进的服务。发电服务 将包括通过原核注射设计和创造转基因和基因靶向小鼠。维修 服务将包括精子冷冻保存、体外受精和菌株重新衍生。在具体目标2中，我们 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, 核心人员将通过评估不断更新用于细胞和鼠标修改的基因编辑工具 目前的文献以及参加研讨会和会议的情况。在具体目标3中，我们建议提供培训 以及与使用遗传模型相关的教育。将对项目负责人和其他用户进行高效培训 并准确地生产转基因小鼠的实验队列，我们将教育用户潜在的 在使用这类模型时经常遇到的问题。核心人员也将对研究进行教育 UAMS和阿肯色州其他校园的社区，了解通过 遗传模型的核心。拟议的CMDR的科学主题是，导致恶化的条件 对骨架的研究具有分子基础，其鉴定将指导特定和有效的开发 治疗。遗传模型核心与这一主题是一致的，因为它将允许项目负责人快速 并有效地测试特定的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.