This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Electron microscopy and electron tomography is being utilized at NCMIR to analyze the structural abnormalities associated with vinculin KO mice. Vinculin is a ubiquitously expressed multiliganded protein that links the actin cytoskeleton to the cell membrane. Metavinculin (MVin), its muscle-specific splice variant isoform, is found to be mutated in patients with dilated cardiomyopathies. In myocytes, it is localized in protein complexes which anchor the contractile apparatus to the sarcolemma. Vinculin is found at intercalated discs (ICDs) as well as in cell-to matrix adhesions. Its function in the myocardium remains poorly understood. Therefore, we developed a mouse model with cardiac-myocyte-specific inactivation of the vinculin (Vcl) gene by using Cre-loxP technology. Since global knockout (KO) of vinculin is embryonic lethal and heterozygous global knockout of vinculin predispose to stress-induced cardiomyopathy, we generated cardiac-myocyte specific vinculin KO mice. Floxed Vin exon 3 excision was mediated by myosin light chain-2 ventricular (MLC2v) Cre recombinase expression.
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