Core--Mutant Mice

靶向P450基因破坏和/或过度表达是该项目努力提供P450酶在肾脏生理或病理生理中所起作用的分子描述的重要组成部分。这些努力取得成功的关键是项目研究人员及时和不受限制地访问P450突变小鼠。动物核心（core D）的总体目标是集中维护、繁殖和初步表征携带P450突变的小鼠品系，这些突变是由靶向基因破坏引起的。预期拟议的集中将大大节省时间和金钱，导致更有效地利用共同资源和专门知识，并提高总体生产力和可重复性。具体来说，Core D将收到来自Project 2的育种对，其中包含编码不同P450亚型的基因突变拷贝。配子、回交和育种技术将用于产生携带129SvJ或C57BL/6J遗传背景的同源（+/+）和（-/-）基因型小鼠。Core D还将对携带P450基因型突变的小鼠进行初步形态学和功能评估。将这些常规任务集中在核心D将消除不必要和昂贵的重复，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（-/-）小鼠已经在129/SvJ背景下可用

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.