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.