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基因破坏和/或过表达是计划项目努力的重要组成部分，以提供P450酶在肾脏生理或病理生理学中扮演的角色的分子描述。对于这些努力的成功至关重要的是计划项目调查人员及时且不受限制地进入P450突变小鼠。动物核心（核心D）的总体目标是将携带P450突变的小鼠菌株的维持，繁殖和初始表征集中，这些菌株受到靶向基因的破坏引起的P450突变。预计拟议的集中化将节省大量的时间和金钱，从而更有效地利用共同资源和专业知识，并提高整体生产率和可重复性。具体而言，核心D将从项目2个育种对中接收，其中包含编码不同P450同工型的基因的突变拷贝。垫料，反向交叉和育种技术将用于产生先天性（+/+），以及（ - / - ）携带129SVJ或C57BL/6J遗传背景的小鼠基因型。核心D还将对携带突变P450基因型的小鼠进行初始形态和功能评估。这些常规任务在核心D中的集中化将消除不必要和昂贵的重复，并将为1-4提供及时的功能研究所需的突变动物。 CYP4A14（ - / - ）和4A10（ - / - ）小鼠已经有129/SVJ背景可用，并且 CYP 4A14（ - / - ）也在先天性C57BL/6J背景中。 CYP4A12无效突变体将在接下来的12-15个月内提供。 CYP2C44（ - / - ）小鼠将在未来2 - 3年内开发，而CYP4A12和2C44转基因在3 - 4年内。