CORE--MUTANT MOUSE

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DESCRIPTION: (adapted from applicant?s abstract) The objective of the Mutant Mouse Core is to centralize maintenance and breeding of mice with various induced mutations generated by gene targeting (gene knockout mice), gene addition (transgenic mice), and gene combinations. Currently, the core has available gene knockout mice for the following genes: neuronal nitric oxide synthase (nNOS or NOS1), inducible nitric oxide synthase (iNOS or NOS2), endothelial nitric oxide synthase (eNOS or NOS3), B2 bradykinin receptor (B2), and the angiotensin II type 2 receptor (AT2). The core also has available mice with two of the three NOS isoforms knocked out in each pairwise combination (e/iNOS, e/nNOS, and i/nNOS). A colony of transgenic mice with brain natriuretic peptide promoter-driven luciferase expression (BNP-Luc) is available. Founders for transgenic mice expressing human angiotensin II (Ang II) in the heart have been generated and additional transgenic mouse strains expressing Ang II in the heart will be imported. Transgenic founders expressing bovine eNOS in the thick ascending limb of the loop of Henle have been generated. In addition, the Core will import gene knockout mice for tissue kallikrein (TK), and PGE2 receptor type 2 and type 3 (EP2 and EP3 respectively). The Core will also create various combinations of gene knockout and transgenic mice, and provide appropriate controls if they are not commercially available. The choice of appropriate controls is determined for each mutant so that their genetic background will be as close to the experimental mice as possible. The Core is responsible for providing expert advice to participating investigators and setting up breeding schemes to generate the required numbers of experimental mice and controls. In addition, the core will determine the relevant genotypes of all weanlings by PCR. Mice which are not of a uniform inbred genetic background will often be backcrossed to strain C57BL/6J (B6) until congenic status is reached (a minimum of 10 backcross generations). The congenic mice will be bred to provide experimental animals for the investigators. (End of abstract)