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 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.
Bartlett
Heather L
HL
Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242-1109, USA.
Sutherland
Lillian
L
Kolker
Sandra J
SJ
Welp
Chelsea
C
Tajchman
Urszula
U
Desmarais
Vera
V
Weeks
Daniel L
DL
D000818:Animals; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006330:Heart Defects, Congenital / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D006720:Homozygote; D006801:Humans; D018715:Microscopy, Video; D008957:Models, Genetic; D009154:Mutation; D009200:Myocardial Contraction; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics* / Q000502:physiology*; D014982:Xenopus laevis
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C092720:NKX2-5 protein, Xenopus; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D029867:Xenopus Proteins