Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart
| Autor: | Rebecca Cochran, Suk D. Regmi, Patrick Y. Jay, Megan T Danzo, Julia B. Winston, Alayna K Hutchinson, David B. Wilson, Claire E. Schulkey, Iuan-Bor D. Chen, Diana Salm, Adam A Panzer, DePorres Cormier |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Heart Septal Defects
Ventricular 0301 basic medicine congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Article Sarcospan Homeobox protein Nkx-2.5 Gene Knockout Techniques Mice 03 medical and health sciences Internal medicine medicine Animals Humans Ventricular outflow tract Myocyte Myocytes Cardiac Heart septal defect Multidisciplinary Genetic interaction business.industry Incidence Membrane Proteins medicine.disease Cardiac malformations Neoplasm Proteins Disease Models Animal 030104 developmental biology Membrane protein Mutation Homeobox Protein Nkx-2.5 cardiovascular system Cardiology Carrier Proteins business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep46438 |
| Popis: | The muscular ventricular septum separates the flow of oxygenated and de-oxygenated blood in air-breathing vertebrates. Defects within it, termed muscular ventricular septal defects (VSDs), are common, yet less is known about how they arise than rarer heart defects. Mutations of the cardiac transcription factor NKX2-5 cause cardiac malformations, including muscular VSDs. We describe here a genetic interaction between Nkx2-5 and Sarcospan (Sspn) that affects the risk of muscular VSD in mice. Sspn encodes a protein in the dystrophin-glycoprotein complex. Sspn knockout (SspnKO) mice do not have heart defects, but Nkx2-5+/−/SspnKO mutants have a higher incidence of muscular VSD than Nkx2-5+/− mice. Myofibers in the ventricular septum follow a stereotypical pattern that is disrupted around a muscular VSD. Subendocardial myofibers normally run in parallel along the left ventricular outflow tract, but in the Nkx2-5+/−/SspnKO mutant they commonly deviate into the septum even in the absence of a muscular VSD. Thus, Nkx2-5 and Sspn act in a pathway that affects the alignment of myofibers during the development of the ventricular septum. The malalignment may be a consequence of a defect in the coalescence of trabeculae into the developing ventricular septum, which has been hypothesized to be the mechanistic basis of muscular VSDs. |
| Databáze: | OpenAIRE |
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