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Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles
The fundamental importance of the proteoglycan versican to early heart formation was clearly demonstrated by the Vcan null mouse called heart defect (hdf). Total absence of the Vcan gene halts heart development at a stage prior to the heart’s pulmonary/aortic outlet segment growth. This creates a pr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930639/ https://www.ncbi.nlm.nih.gov/pubmed/24586547 http://dx.doi.org/10.1371/journal.pone.0089133 |
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author | Burns, Tara A. Dours-Zimmermann, Maria T. Zimmermann, Dieter R. Krug, Edward L. Comte-Walters, Susana Reyes, Leticia Davis, Monica A. Schey, Kevin L. Schwacke, John H. Kern, Christine B. Mjaatvedt, Corey H. |
author_facet | Burns, Tara A. Dours-Zimmermann, Maria T. Zimmermann, Dieter R. Krug, Edward L. Comte-Walters, Susana Reyes, Leticia Davis, Monica A. Schey, Kevin L. Schwacke, John H. Kern, Christine B. Mjaatvedt, Corey H. |
author_sort | Burns, Tara A. |
collection | PubMed |
description | The fundamental importance of the proteoglycan versican to early heart formation was clearly demonstrated by the Vcan null mouse called heart defect (hdf). Total absence of the Vcan gene halts heart development at a stage prior to the heart’s pulmonary/aortic outlet segment growth. This creates a problem for determining the significance of versican’s expression in the forming valve precursors and vascular wall of the pulmonary and aortic roots. This study presents data from a mouse model, Vcan ((tm1Zim)), of heart defects that results from deletion of exon 7 in the Vcan gene. Loss of exon 7 prevents expression of two of the four alternative splice forms of the Vcan gene. Mice homozygous for the exon 7 deletion survive into adulthood, however, the inability to express the V2 or V0 forms of versican results in ventricular septal defects, smaller cushions/valve leaflets with diminished myocardialization and altered pulmonary and aortic outflow tracts. We correlate these phenotypic findings with a large-scale differential protein expression profiling to identify compensatory alterations in cardiac protein expression at E13.5 post coitus that result from the absence of Vcan exon 7. The Vcan ((tm1Zim)) hearts show significant changes in the relative abundance of several cytoskeletal and muscle contraction proteins including some previously associated with heart disease. These alterations define a protein fingerprint that provides insight to the observed deficiencies in pre-valvular/septal cushion mesenchyme and the stability of the myocardial phenotype required for alignment of the outflow tract with the heart ventricles. |
format | Online Article Text |
id | pubmed-3930639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39306392014-02-25 Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles Burns, Tara A. Dours-Zimmermann, Maria T. Zimmermann, Dieter R. Krug, Edward L. Comte-Walters, Susana Reyes, Leticia Davis, Monica A. Schey, Kevin L. Schwacke, John H. Kern, Christine B. Mjaatvedt, Corey H. PLoS One Research Article The fundamental importance of the proteoglycan versican to early heart formation was clearly demonstrated by the Vcan null mouse called heart defect (hdf). Total absence of the Vcan gene halts heart development at a stage prior to the heart’s pulmonary/aortic outlet segment growth. This creates a problem for determining the significance of versican’s expression in the forming valve precursors and vascular wall of the pulmonary and aortic roots. This study presents data from a mouse model, Vcan ((tm1Zim)), of heart defects that results from deletion of exon 7 in the Vcan gene. Loss of exon 7 prevents expression of two of the four alternative splice forms of the Vcan gene. Mice homozygous for the exon 7 deletion survive into adulthood, however, the inability to express the V2 or V0 forms of versican results in ventricular septal defects, smaller cushions/valve leaflets with diminished myocardialization and altered pulmonary and aortic outflow tracts. We correlate these phenotypic findings with a large-scale differential protein expression profiling to identify compensatory alterations in cardiac protein expression at E13.5 post coitus that result from the absence of Vcan exon 7. The Vcan ((tm1Zim)) hearts show significant changes in the relative abundance of several cytoskeletal and muscle contraction proteins including some previously associated with heart disease. These alterations define a protein fingerprint that provides insight to the observed deficiencies in pre-valvular/septal cushion mesenchyme and the stability of the myocardial phenotype required for alignment of the outflow tract with the heart ventricles. Public Library of Science 2014-02-20 /pmc/articles/PMC3930639/ /pubmed/24586547 http://dx.doi.org/10.1371/journal.pone.0089133 Text en © 2014 Burns et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Burns, Tara A. Dours-Zimmermann, Maria T. Zimmermann, Dieter R. Krug, Edward L. Comte-Walters, Susana Reyes, Leticia Davis, Monica A. Schey, Kevin L. Schwacke, John H. Kern, Christine B. Mjaatvedt, Corey H. Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles |
title | Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles |
title_full | Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles |
title_fullStr | Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles |
title_full_unstemmed | Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles |
title_short | Imbalanced Expression of Vcan mRNA Splice Form Proteins Alters Heart Morphology and Cellular Protein Profiles |
title_sort | imbalanced expression of vcan mrna splice form proteins alters heart morphology and cellular protein profiles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930639/ https://www.ncbi.nlm.nih.gov/pubmed/24586547 http://dx.doi.org/10.1371/journal.pone.0089133 |
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