for the generation of transgenic and knockout animals but the core will also support the individual projects in the initial characterization studies on the transgenic and knockout models. The characterization of each mouse model will include careful analysis of the expression pattern of the transgene and pathological and physiological changes, which occur as a result of transgene expression. The PI, Dr. Marks, Marx and Kass have collaborated over the past few years on the generation and characterization of the MK24=MinK-KVLQTl transgenic mouse (1) and FKBP12.6 knockout mice (2, 3). Physiological characterization of transgenic mice requires the technical expertise that is present in the laboratory of the core (4-6). Over the past three years systems have been set up in the laboratory to allow us to perform such studies. ' The core will provide support for the PPG in the following areas: ? A. The preparation and maintenance of transgenic and knockout mice B. Characterization of transgenic and knock-out mice including -preparation and analysis of tissue specimens from animals C. Baseline physiological measurements including hemodynamics and echocardiography D. Physiological measurements on transgenic and knockout mice for drug testing. ? Myocardial infarction and aortic banding when necessary F. Blood Pressure Measurements G. Maintenance of Cell CultureLines A major goal of the Animal Models and Tissue Culture Core is to develop and test animal models to provide models in which to examine allosteric interactions in ion channels. This Core will fill an essential and exciting role of the Columbia University PPG by facilitating the use of genetic models in animals using state-of-the-art techniques to make physiological measurements (eg,.ECG recording, EPS, echocardiograms and hemodynamic measurements) in mice. Finally, we will maintain all cell lines and develop stable transfected cell lines for the various constructs to be investigated. A stable cell line transfected with a wild-type expressing BK.channel has already been developed by Dr. Marx. Table 1. Mouse models used by each project Project 1-Karlin Project 2-Marks Project 3-Kass Project 4-Marx **(Tissue Culture) **(Tissue Culture) **(Tissue Culture) ***GuineaPigs J32AR* X X RyR2-S2809A* X X MK24* X FKBP12.6KO* X KCNQ1-L2M LAD Ligation X Model* Future models RyR2-ARVD2 X RyR2-CPVT X BKa knockout X RyR2-S2809D* X 32AR knockout X PHS 398/2590 (Rev. 05/01) Page 273 Continuation Format Page'
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