Transgenic and Knockout Mouse Core

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Overview The three projects in the Program will make extensive use of a variety of genetic approaches to study the role of adhesive-related candidate genes in cardiac function. In certain cases, murine transgenic approaches will be used to direct expression of desired genes via well-defined cardiac-specific promoters (e.g. myosin light chain 2 ventricular, oc-Myosin heavy chain (Chen et al., 1998a; Chen et al., 1998b; Ross et al., 1996; Yasukawa et al., 2003). In addition, gene-targeting approaches will be utilized to generate "knockout" of a candidate gene, or "knock-in" of a specific lesion into the murine genome so that the functional role of a specific mutation can be examined in its native context (Bang et al., 2006; Chen et al., 1998a; Chen et al., 1998b; Shai et al., 2002; Zhou et al., 2001) . Standard transgenesis and gene-targeting strategies (via homologous recombination in ES cells) are currently fully operative in our Program. The Chen, Knowlton, and Ross labs have extensive experience in the generation, identification, breeding, and characterization of both transgenic and gene-targeted mouse models of cardiac development and disease (Chen et al., 1998a; Chen et al., 1998b; Chu et al., 2000a; Ding et al., 2004; Huang et al., 2003a; Huang et al., 2003b; Li et al., 2005; Liang et al., 2005; Ross et al., 1996; Shai et al., 2002; Trifilo et al., 2006; Xu et al., 2005; Yasukawa et al., 2003; Zhou et al., 2001). Core Unit C will Founder mice will be identified, bred, and maintained in a core animal facility at UCSD. Core C will also be responsible for distributing the mice utilized throughout the program to each individual project and other core units. The objectives of this Core Unit are as follows: 1) To provide services to assist in the design of the appropriate transgenic or gene-targeting constructs necessary for production of mouse models, 2) To generate transgenic and gene-targeted mice, 3) To breed and maintain appropriate lines of genetically-manipulated mice for various projects within the Program, and 4) To generate and breed lines of mice required for regionally restricted and/or tissue-specific conditional gene targeting and over-expression via Cre-lox strategies.