Targeted P450-gene disruption and/or over-expression is an important component of the PPG 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 PPG 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 utilize matting and breeding techniques for the maintenance, expansion, and generation of congenic (+/+) and (-/-) mice genotypes carrying either 129SvJ or C57BL/6J genetic backgrounds. Core D will also perform the inifial morphological and funcfional evaluation of mice carrying mutated P450 genotypes. The centralization of these routine tasks in Core D will eliminate unnecessary and cosfiy duplications and will provide projects 1-4 with the mutant animals needed for funcfional studies in a fimely fashion. The availability of mouse models of p450 gene dysfunction will provide the PPG invesfigators with unique animal models for their studies of physiological and pathophysiological roles of the epoxygenase and w-hydroxylase branches of the renal arachidonate monooxygenase pathway
Hypertension is a major cause of renal and cardiovascular morbidity and mortality, an new strategies for its early diagnosis and treatment are needed to prevent the consequences of untreated chronic hypertension. Core D serves as the depository of mouse models of experimental hypertension that are to be utilized by PPG investigators in their studies of the molecular causes of this devastafing disease.
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