Core--Mutant Mice

核心——突变小鼠

• 批准号: 7459647
• 负责人: JORGE CAPDEVILA
• 金额: $ 21.23万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7459647
• 关键词: Age; Alleles; Animals; Appearance; Backcrossings; Blood Chemical Analysis; Blood Pressure; Blood Vessels; Breeding; Chemistry; Code; Congenic Mice; Creatinine; Cytochrome P450; Disruption; Enzymes; Evaluation; Functional disorder; Gene Targeting; Generations; Genes; Genetic; Genotype; Goals; Individual; Induced Mutation; Kidney; Lead; Lesion; Maintenance; Methods; Microscopic; Molecular; Morphology; Mouse Strains; Mus; Mutant Strains Mice; Mutate; Mutation; Numbers; Phenotype; Physiological; Physiology; Productivity; Protein Isoforms; Protein Overexpression; Reproducibility; Research Personnel; Resources; Role playing therapy; Savings; Secure; Serum; Shapes; Standards of Weights and Measures; Techniques; Time; Transgenic Mice; Transgenic Organisms; Tubular formation; Urea Nitrogen; Urine; Weight; animal breeding; congenic; improved; inorganic phosphate; interstitial; mutant; programs; sex; size; success

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.

有针对性的P450基因中断和/或过度表达是该计划项目努力的一个重要组成部分，该计划旨在提供P450酶在肾脏生理或病理生理中所起作用的分子描述。这些努力成功的关键是计划项目调查人员及时和不受限制地获得P450突变小鼠。动物核心(核心D)的总体目标是集中维护、培育和初步鉴定携带靶向基因破坏诱导的P450突变的小鼠品系。预计拟议的集中管理将大大节省时间和资金，更有效地利用共同资源和专门知识，并提高整体生产率和可重复性。具体地说，核心D将从项目2接收包含编码不同P450亚型的基因突变副本的繁殖者对。将利用垫子、回交和育种技术产生携带129SvJ或C57BL/6J遗传背景的同源(+/+)和(-/-)小鼠。CORE D还将对携带突变P450基因的小鼠进行初步的形态和功能评估。将这些例行任务集中在核心D将消除不必要和昂贵的重复工作，并将及时为项目1-4提供进行功能研究所需的突变动物。Cyp4a14(-/-)和4a10(-/-)小鼠已经在129/SVJ背景下提供，并且 CYP 4a14(-/-)也是C57BL/6J的同源基因。Cyp4a12零突变体将在未来12-15个月内推出。Cyp2c44(-/-)小鼠将在未来2-3年内发育，Cyp4a12和2c44转基因小鼠将在3-4年内发育。