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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL046345-18
Application #
7905101
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2009-07-01
Project End
2012-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
18
Fiscal Year
2009
Total Cost
$310,717
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Dewan, Sukriti; McCabe, Kimberly J; Regnier, Michael et al. (2016) Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study. J Phys Chem B 120:8264-75
Peter, Angela K; Bradford, William H; Dalton, Nancy D et al. (2016) Increased Echogenicity and Radiodense Foci on Echocardiogram and MicroCT in Murine Myocarditis. PLoS One 11:e0159971
Sheikh, Farah; Lyon, Robert C; Chen, Ju (2015) Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease. Gene 569:14-20
Israeli-Rosenberg, Sharon; Chen, Chao; Li, Ruixia et al. (2015) Caveolin modulates integrin function and mechanical activation in the cardiomyocyte. FASEB J 29:374-84
Bang, Marie-Louise; Gu, Yusu; Dalton, Nancy D et al. (2014) The muscle ankyrin repeat proteins CARP, Ankrd2, and DARP are not essential for normal cardiac development and function at basal conditions and in response to pressure overload. PLoS One 9:e93638
Israeli-Rosenberg, Sharon; Manso, Ana Maria; Okada, Hideshi et al. (2014) Integrins and integrin-associated proteins in the cardiac myocyte. Circ Res 114:572-586
Stroud, Matthew J; Banerjee, Indroneal; Veevers, Jennifer et al. (2014) Linker of nucleoskeleton and cytoskeleton complex proteins in cardiac structure, function, and disease. Circ Res 114:538-48
Zemljic-Harpf, Alice E; Godoy, Joseph C; Platoshyn, Oleksandr et al. (2014) Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin-43-containing gap junctions in cardiac myocytes. J Cell Sci 127:1104-16
Lyon, Robert C; Mezzano, Valeria; Wright, Adam T et al. (2014) Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model. Hum Mol Genet 23:1134-50
Pfeiffer, E R; Wright, A T; Edwards, A G et al. (2014) Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing. J Mol Cell Cardiol 76:265-74

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