Cardiovascular defects in a mouse model of HOXA1 syndrome
Congenital heart disease is one of the most common human birth defects, yet many genes and pathways regulating heart development remain unknown. A recent study in humans revealed that mutations in a single Hox gene, HOXA1 (Athabascan Brainstem Dysgenesis Syndrome, Bosley-Salih-Alorainy Syndrome), ca...
Published in: | Human Molecular Genetics |
---|---|
Main Authors: | , |
Format: | Text |
Language: | English |
Published: |
Oxford University Press
2012
|
Subjects: | |
Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235008 http://www.ncbi.nlm.nih.gov/pubmed/21940751 https://doi.org/10.1093/hmg/ddr434 |
id |
ftpubmed:oai:pubmedcentral.nih.gov:3235008 |
---|---|
record_format |
openpolar |
spelling |
ftpubmed:oai:pubmedcentral.nih.gov:3235008 2023-05-15T15:26:10+02:00 Cardiovascular defects in a mouse model of HOXA1 syndrome Makki, Nadja Capecchi, Mario R. 2012-01-01 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235008 http://www.ncbi.nlm.nih.gov/pubmed/21940751 https://doi.org/10.1093/hmg/ddr434 en eng Oxford University Press http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235008 http://www.ncbi.nlm.nih.gov/pubmed/21940751 http://dx.doi.org/10.1093/hmg/ddr434 © The Author 2011. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. Articles Text 2012 ftpubmed https://doi.org/10.1093/hmg/ddr434 2013-09-03T23:46:24Z Congenital heart disease is one of the most common human birth defects, yet many genes and pathways regulating heart development remain unknown. A recent study in humans revealed that mutations in a single Hox gene, HOXA1 (Athabascan Brainstem Dysgenesis Syndrome, Bosley-Salih-Alorainy Syndrome), can cause severe cardiovascular malformations, some of which are lethal without surgical intervention. Since the discovery of the human syndromes, there have been no reports of any Hox mouse mutants with cardiac defects, hampering studies to explore the developmental causes of the human disease. In this study, we identify severe cardiovascular malformations in a Hox mouse model, which mimic the congenital heart defects in HOXA1 syndrome patients. Hoxa1 null mice show defects such as interrupted aortic arch, aberrant subclavian artery and Tetralogy of Fallot, demonstrating that Hoxa1 is required for patterning of the great arteries and outflow tract of the heart. We show that during early embryogenesis, Hoxa1 is expressed in precursors of cardiac neural crest cells (NCCs), which populate the heart. We further demonstrate that Hoxa1 acts upstream of several genes, important for neural crest specification. Thus, our data allow us to suggest a model in which Hoxa1 regulates heart development through its influence on cardiac NCCs, providing insight into the mechanisms underlying the human disease. Text Athabascan PubMed Central (PMC) Human Molecular Genetics 21 1 26 31 |
institution |
Open Polar |
collection |
PubMed Central (PMC) |
op_collection_id |
ftpubmed |
language |
English |
topic |
Articles |
spellingShingle |
Articles Makki, Nadja Capecchi, Mario R. Cardiovascular defects in a mouse model of HOXA1 syndrome |
topic_facet |
Articles |
description |
Congenital heart disease is one of the most common human birth defects, yet many genes and pathways regulating heart development remain unknown. A recent study in humans revealed that mutations in a single Hox gene, HOXA1 (Athabascan Brainstem Dysgenesis Syndrome, Bosley-Salih-Alorainy Syndrome), can cause severe cardiovascular malformations, some of which are lethal without surgical intervention. Since the discovery of the human syndromes, there have been no reports of any Hox mouse mutants with cardiac defects, hampering studies to explore the developmental causes of the human disease. In this study, we identify severe cardiovascular malformations in a Hox mouse model, which mimic the congenital heart defects in HOXA1 syndrome patients. Hoxa1 null mice show defects such as interrupted aortic arch, aberrant subclavian artery and Tetralogy of Fallot, demonstrating that Hoxa1 is required for patterning of the great arteries and outflow tract of the heart. We show that during early embryogenesis, Hoxa1 is expressed in precursors of cardiac neural crest cells (NCCs), which populate the heart. We further demonstrate that Hoxa1 acts upstream of several genes, important for neural crest specification. Thus, our data allow us to suggest a model in which Hoxa1 regulates heart development through its influence on cardiac NCCs, providing insight into the mechanisms underlying the human disease. |
format |
Text |
author |
Makki, Nadja Capecchi, Mario R. |
author_facet |
Makki, Nadja Capecchi, Mario R. |
author_sort |
Makki, Nadja |
title |
Cardiovascular defects in a mouse model of HOXA1 syndrome |
title_short |
Cardiovascular defects in a mouse model of HOXA1 syndrome |
title_full |
Cardiovascular defects in a mouse model of HOXA1 syndrome |
title_fullStr |
Cardiovascular defects in a mouse model of HOXA1 syndrome |
title_full_unstemmed |
Cardiovascular defects in a mouse model of HOXA1 syndrome |
title_sort |
cardiovascular defects in a mouse model of hoxa1 syndrome |
publisher |
Oxford University Press |
publishDate |
2012 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235008 http://www.ncbi.nlm.nih.gov/pubmed/21940751 https://doi.org/10.1093/hmg/ddr434 |
genre |
Athabascan |
genre_facet |
Athabascan |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235008 http://www.ncbi.nlm.nih.gov/pubmed/21940751 http://dx.doi.org/10.1093/hmg/ddr434 |
op_rights |
© The Author 2011. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
op_doi |
https://doi.org/10.1093/hmg/ddr434 |
container_title |
Human Molecular Genetics |
container_volume |
21 |
container_issue |
1 |
container_start_page |
26 |
op_container_end_page |
31 |
_version_ |
1766356708702027776 |