Transient early embryonic expression of Nkx2‐5 mutations linked to congenital heart defects in human causes heart defects in Xenopus laevis

Nkx2‐5 is a homeobox containing transcription factor that is conserved and expressed in organisms that form hearts. Fruit flies lacking the gene (tinman) fail to form a dorsal vessel, mice that are homozygous null for Nkx2‐5 form small, deformed hearts, and several human cardiac defects have been li...

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Bibliographic Details
Published in:Developmental dynamics 2007-09, Vol.236 (9), p.2475-2484
Main Authors: Bartlett, Heather L., Sutherland, Lillian, Kolker, Sandra J., Welp, Chelsea, Tajchman, Urszula, Desmarais, Vera, Weeks, Daniel L.
Format: Article
Language:English
Subjects:
Animals
Drosophila
Gene Deletion
Gene Expression Regulation, Developmental
Heart Defects, Congenital - genetics
heart development
Homeobox Protein Nkx-2.5
Homeodomain Proteins - genetics
Homeodomain Proteins - physiology
Homozygote
Humans
Microscopy, Video
Models, Genetic
Mutation
Myocardial Contraction
Nkx2‐5
Point Mutation
Protein Structure, Tertiary
Transcription Factors - genetics
Transcription Factors - physiology
Xenopus
Xenopus laevis
Xenopus Proteins - genetics
Xenopus Proteins - physiology
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Summary:Nkx2‐5 is a homeobox containing transcription factor that is conserved and expressed in organisms that form hearts. Fruit flies lacking the gene (tinman) fail to form a dorsal vessel, mice that are homozygous null for Nkx2‐5 form small, deformed hearts, and several human cardiac defects have been linked to dominant mutations in the Nkx2‐5 gene. The Xenopus homologs (XNkx2‐5) of two truncated forms of Nkx2‐5 that have been identified in humans with congenital heart defects were used in the studies reported here. mRNAs encoding these mutations were injected into single cell Xenopus embryos, and heart development was monitored. Our results indicate that the introduction of truncated XNkx2‐5 variants leads to three principle developmental defects. The atrial septum and the valve of the atrioventricular canal were both abnormal. In addition, video microscopic timing of heart contraction indicated that embryos injected with either mutant form of XNkx2‐5 have conduction defects. Developmental Dynamics 236:2475–2484, 2007. © 2007 Wiley‐Liss, Inc.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.21244