| Biallelic expression of Tbx1 protects the embryo against developmental defects caused by increased receptor tyrosine kinase signalling. | |
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MedLine Citation:
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PMID: 22674535 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans, characterised by cardiovascular defects such as interrupted aortic arch, outflow tract defects, thymus and parathyroid hypo- or aplasia and cleft palate. Heterozygosity of Tbx1, the mouse homologue of the candidate TBX1 gene, results in mild defects dependent on genetic background, whereas complete inactivation results in severe malformations in multiple tissues. RESULTS: The loss of function mutations in two Sprouty genes, which encode feedback antagonists of receptor tyrosine kinase (RTK) signaling, phenocopy many defects associated with the syndrome in the mouse. The stepwise reduction of Sprouty gene dosage resulted in different phenotypes emerging at specific steps, suggesting that the threshold up to which a given developmental process can tolerate increased RTK signaling is different. Tbx1 heterozygosity significantly exacerbated the severity of all these defects, which correlated with a substantial increase in RTK signaling. CONCLUSIONS: Our findings suggest that TBX1 functions as an essential component of a mechanism that protects the embryo against perturbations in RTK signaling that may lead to developmental defects characteristic of 22q11.2 deletion syndrome. We propose that genetic factors that enhance RTK signalling ought to be considered as potential genetic modifiers of this syndrome. |
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Authors:
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Subreena Simrick; Dorota Szumska; Jennifer R Gardiner; Kieran Jones; Karun Sagar; Bernice Morrow; Shoumo Bhattacharya; M Albert Basson |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-6 |
Journal Detail:
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Title: Developmental dynamics : an official publication of the American Association of Anatomists Volume: - ISSN: 1097-0177 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9201927 Medline TA: Dev Dyn Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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Department of Craniofacial Development and Stem Cell Biology, King's College London, 27th floor, Guy's Tower, London SE1 9RT, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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