Core--Mouse Genetics

核心--小鼠遗传学

• 批准号: 6925208
• 负责人: PAMELA L MELLON
• 金额: $ 26.16万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925208
• 关键词: animal breeding; biomedical facility; biotechnology; environmental toxicology; gene environment interaction; gene expression; gene targeting; genetic strain; genetically modified animals; hazardous substances; laboratory mouse; model design /development; molecular genetics

DESCRIPTION (provided by applicant): It is clear that the progress of toxicological Superfund research during the coming decade will depend upon the mouse as an experimental model to investigate both basic and clinically relevant questions. The high degree of conservation in the genomes of humans and mice makes the approach of using transgene and knock-out gene technology to create models for human toxicology extremely attractive. At the same time, unique differences in metabolism and response to toxic chemicals between mouse and human make the substitution of human genes into the mouse compelling. This core provides this Superfund projects with the most advanced technologies for genetic modification of the mouse genome. Transgenic mice carrying new or novel genes and 'Knock-out' or 'Knock-in' mice lacking specific genes of interest or containing modified version of key genes are created. Conditional expression and Cre/LoxP targeted knock-out strategies are provided. The core provides a wide array of technology- and expertise-intensive services including experimental design consultation, embryonic stem cell homologous recombination, Cre transfection of embryonic stem cells for LoxP excision, blastocyst microinjection of genetically altered embryonic stem cells into blastocysts to create knock-out or knock-in mice, pronuclear injection of transgenes or bacterial artificial chromosomes to create transgenic mice, embryo injecion of Lentivirus vectors, cryopreservation of embryos, and fertility interventions such as in vitro fertilization and ovary transplant. Services are tailored for the projects with special service and high priority. This core is an outstanding example of how extraordinarily specialized techniques, highly trained dedicated personnel, and expensive equipment can be accessed by researchers who could not reasonably expect to develop them on an individual basis. The availability of this Transgenic and Knock-out Mouse Core will enable the projects to conduct versatile, cutting-edge, molecular genetic research in the mouse with a battery of multidisciplinary state-of-the-art techniques.

描述（由申请人提供）：很明显，在未来十年中，毒理学超级基金研究的进展将取决于小鼠作为实验模型来研究基本和临床相关问题。人类和小鼠基因组的高度保守性使得利用转基因和基因敲除技术来建立人类毒理学模型的方法极具吸引力。 与此同时，小鼠和人类在代谢和对有毒化学物质的反应方面的独特差异使得将人类基因替换到小鼠中变得引人注目。该核心为超级基金项目提供了最先进的小鼠基因组遗传修饰技术。产生携带新的或新颖基因的转基因小鼠和缺乏感兴趣的特定基因或含有关键基因的修饰形式的“敲除”或“敲入”小鼠。提供了条件表达和Cre/LoxP靶向敲除策略。 核心提供广泛的技术和专业知识密集型服务，包括实验设计 咨询，胚胎干细胞同源重组，Cre转染胚胎干细胞用于LoxP切除，将遗传改变的胚胎干细胞显微注射到胚泡中以产生敲除或敲入小鼠，原核注射转基因或细菌人工染色体以产生转基因小鼠，慢病毒载体的胚胎注射，胚胎冷冻保存，以及诸如体外受精和卵巢移植等生育干预措施。 为具有特殊服务和高优先级的项目量身定制服务。 这个核心是一个杰出的例子，说明了那些无法合理地期望在个人基础上开发它们的研究人员如何能够获得非常专业的技术、训练有素的专门人员和昂贵的设备。 这种转基因和敲除小鼠核心的可用性将使项目能够通过一系列多学科的最先进技术在小鼠中进行多功能，尖端的分子遗传学研究。