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Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development
Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascul...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852499/ https://www.ncbi.nlm.nih.gov/pubmed/26822476 http://dx.doi.org/10.1242/dmm.022053 |
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author | Baardman, Maria E. Zwier, Mathijs V. Wisse, Lambertus J. Gittenberger-de Groot, Adriana C. Kerstjens-Frederikse, Wilhelmina S. Hofstra, Robert M. W. Jurdzinski, Angelika Hierck, Beerend P. Jongbloed, Monique R. M. Berger, Rolf M. F. Plösch, Torsten DeRuiter, Marco C. |
author_facet | Baardman, Maria E. Zwier, Mathijs V. Wisse, Lambertus J. Gittenberger-de Groot, Adriana C. Kerstjens-Frederikse, Wilhelmina S. Hofstra, Robert M. W. Jurdzinski, Angelika Hierck, Beerend P. Jongbloed, Monique R. M. Berger, Rolf M. F. Plösch, Torsten DeRuiter, Marco C. |
author_sort | Baardman, Maria E. |
collection | PubMed |
description | Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascular development of Lrp2 KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. The Lrp2 KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in the Lrp2 KO. This explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans with LRP2 mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis. |
format | Online Article Text |
id | pubmed-4852499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-48524992016-05-19 Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development Baardman, Maria E. Zwier, Mathijs V. Wisse, Lambertus J. Gittenberger-de Groot, Adriana C. Kerstjens-Frederikse, Wilhelmina S. Hofstra, Robert M. W. Jurdzinski, Angelika Hierck, Beerend P. Jongbloed, Monique R. M. Berger, Rolf M. F. Plösch, Torsten DeRuiter, Marco C. Dis Model Mech Research Article Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascular development of Lrp2 KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. The Lrp2 KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in the Lrp2 KO. This explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans with LRP2 mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis. The Company of Biologists Ltd 2016-04-01 /pmc/articles/PMC4852499/ /pubmed/26822476 http://dx.doi.org/10.1242/dmm.022053 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Baardman, Maria E. Zwier, Mathijs V. Wisse, Lambertus J. Gittenberger-de Groot, Adriana C. Kerstjens-Frederikse, Wilhelmina S. Hofstra, Robert M. W. Jurdzinski, Angelika Hierck, Beerend P. Jongbloed, Monique R. M. Berger, Rolf M. F. Plösch, Torsten DeRuiter, Marco C. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development |
title | Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development |
title_full | Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development |
title_fullStr | Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development |
title_full_unstemmed | Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development |
title_short | Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development |
title_sort | common arterial trunk and ventricular non-compaction in lrp2 knockout mice indicate a crucial role of lrp2 in cardiac development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852499/ https://www.ncbi.nlm.nih.gov/pubmed/26822476 http://dx.doi.org/10.1242/dmm.022053 |
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