Core--Mutant Mice

核心——突变小鼠

• 批准号: 6813201
• 负责人: JORGE CAPDEVILA
• 金额: $ 14.3万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6813201
• 关键词: animal breeding; animal colony; arachidonate; biomedical facility; biotechnology; cytochrome P450; enzyme deficiency; gene targeting; genetic manipulation; genetically modified animals; laboratory mouse; model design /development

Targeted P450-gene disruption and/or over-expression is an important component of the Program Project efforts to provide molecular descriptions of the roles played by the P450 enzymes in renal physiology or pathophysiology. Crucial to the success of these efforts is the timely and unrestricted access by the Program Project investigators to P450 mutant mice. The overall goals of the animal core (Core D) are to centralize the maintenance, breeding, and initial characterization of mice strains carrying P450 mutations induced by targeted gene disruption. It is expected that the proposed centralization will result in significant savings of time and money, lead to a more efficient utilization of common resources and expertise, and improve overall productivity and reproducibility. Specifically, Core D will receive from Project 2 breeder pairs containing mutated copies of genes coding for distinct P450 isoforms. Matting, backcross, and breeding techniques will be utilized for the generation of congenic (+/+), and (-/-) mice genotypes carrying either 129SvJ or C57BL/6J genetic backgrounds. Core D will also perform the initial morphological and functional evaluation of mice carrying mutated P450 genotypes. The centralization of these routine tasks in Core D will eliminate unnecessary and costly duplications and will provide projects 1-4 with the mutant animals needed for functional studies in a timely fashion. Cyp4a14 (-/-) and 4a10 (-/-) mice are already available in 129/SvJ background, and Cyp 4a14 (-/-) also in congenic C57BL/6J background. Cyp4a12 null mutants will available within the next 12-15 months. Cyp2c44 (-/-) mice will be developed within the next 2-3 years, and Cyp4a12 and 2c44 transgenics in years 3-4.

靶向 P450 基因破坏和/或过度表达是该项目努力的一个重要组成部分，该项目努力提供 P450 酶在肾脏生理学或病理生理学中所发挥作用的分子描述。这些努力成功的关键是项目研究人员及时且不受限制地接触 P450 突变小鼠。动物核心 (Core D) 的总体目标是集中对携带由靶向基因破坏诱导的 P450 突变的小鼠品系的维护、育种和初步表征。预计拟议的集中化将大大节省时间和金钱，更有效地利用共同资源和专业知识，并提高整体生产力和可重复性。具体来说，Core D 将从 Project 2 接收包含编码不同 P450 同种型基因突变副本的育种对。将利用交配、回交和育种技术来产生携带 129SvJ 或 C57BL/6J 遗传背景的同源 (+/+) 和 (-/-) 基因型小鼠。 Core D 还将对携带突变 P450 基因型的小鼠进行初步形态和功能评估。这些日常任务集中在核心 D 中将消除不必要且成本高昂的重复，并将及时为项目 1-4 提供功能研究所需的突变动物。 Cyp4a14 (-/-) 和 4a10 (-/-) 小鼠已在 129/SvJ 背景中可用，并且 Cyp 4a14 (-/-) 也在同类 C57BL/6J 背景中。 Cyp4a12 无效突变体将在未来 12-15 个月内上市。 Cyp2c44 (-/-) 小鼠将在未来 2-3 年内培育出来，Cyp4a12 和 2c44 转基因小鼠将在 3-4 年内培育出来。