ROLE OF ANKYRIN B IN CARDIAC DEVELOPMENT & FUNCTION

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Ankyrin-B is a candidate protein to spatially organize IP3 and ryanodine receptors in striated muscles. We have knocked out the gene encoding ankyrin-B in the mouse by homologous recombination, and are now evaluating its consequences for cardiac development. We have found in isolated cardiomyocytes that the IP3 receptor is mis-sorted, and that patterns of calcium release are grossly abnormal. Ankyrin-B depleted hearts of exhibit reduction in ventricular mass, although their ultra structure is essentially normal. The goals of the proposal are to quantitatively assess the effects of ankyrin-B knock out on the volumetric and microstructural composition of the neonate mouse heart by using both conventional 3D and diffusion tensor MR microscopy.