Luma is not essential for murine cardiac development and function
| Autor: | Kirk L. Peterson, Yusu Gu, Xi Fang, Matthew J. Stroud, William H. Bradford, Larry Gerace, Nuno Guimarães-Camboa, Sylvia M. Evans, Nancy D. Dalton, Ju Chen, Jianlin Zhang, Jennifer Veevers |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Physiology LINC complex Myocytes Smooth Muscle Luma Cardiomyopathy Linker of nucleoskeleton to cytoskeleton complex Biology medicine.disease_cause Mechanotransduction Cellular Nuclear envelope Germline 03 medical and health sciences 0302 clinical medicine Physiology (medical) Morphogenesis medicine Animals Humans Myocyte Genetic Predisposition to Disease Myocytes Cardiac Nuclear Matrix Arrhythmogenic Right Ventricular Dysplasia Cells Cultured Cytoskeleton Mice Knockout Pressure overload Mutation Heart development Myocardium Editorials Gene Expression Regulation Developmental Membrane Proteins Outer nuclear membrane Heart Fibroblasts medicine.disease Cell biology Mice Inbred C57BL 030104 developmental biology Inner nuclear membrane Female Hypertrophy Left Ventricular Arrhythmogenic right ventricular cardiomyopathy Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery |
| Zdroj: | Stroud, M J, Fang, X, Zhang, J, Guimaraes-Camboa, N, Veevers, J, Dalton, N D, Gu, Y, Bradford, W H, Peterson, K L, Evans, S M, Gerace, L & Chen, J 2018, ' Luma is not essential for murine cardiac development and function ', Cardiovascular Research, vol. 114, no. 3, pp. 378-388 . https://doi.org/10.1093/cvr/cvx205 |
| ISSN: | 1755-3245 0008-6363 |
| Popis: | AimsLuma is a recently discovered, evolutionarily conserved protein expressed in mammalian heart, which is associated with the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex. The LINC complex structurally integrates the nucleus and the cytoplasm and plays a critical role in mechanotransduction across the nuclear envelope. Mutations in several LINC components in both humans and mice result in various cardiomyopathies, implying they play essential, non-redundant roles. A single amino acid substitution of serine 358 to leucine (S358L) in Luma is the unequivocal cause of a distinct form of arrhythmogenic cardiomyopathy. However, the role of Luma in heart has remained obscure. In addition, it also remains to be determined how the S358L mutation in Luma leads to cardiomyopathy.Methods and resultsTo determine the role of Luma in the heart, we first determined the expression pattern of Luma in mouse heart. Luma was sporadically expressed in cardiomyocytes throughout the heart, but was highly and uniformly expressed in cardiac fibroblasts and vascular smooth muscle cells. We also generated germline null Luma mice and discovered that germline null mutants were viable and exhibited normal cardiac function. Luma null mice also responded normally to pressure overload induced by transverse aortic constriction. In addition, localization and expression of other LINC complex components in both cardiac myocytes and fibroblasts was unaffected by global loss of Luma. Furthermore, we also generated and characterized Luma S358L knock-in mice, which displayed normal cardiac function and morphology.ConclusionOur data suggest that Luma is dispensable for murine cardiac development and function and that the Luma S358L mutation alone may not cause cardiomyopathy in mice. |
| Databáze: | OpenAIRE |
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