Irx3 is required for postnatal maturation of the mouse ventricular conduction system

Scientific Reports
Kyoung-Han KimPeter H Backx

Abstract

The ventricular conduction system (VCS) orchestrates the harmonious contraction in every heartbeat. Defects in the VCS are often associated with life-threatening arrhythmias and also promote adverse remodeling in heart disease. We have previously established that the Irx3 homeobox gene regulates rapid electrical propagation in the VCS by modulating the transcription of gap junction proteins Cx40 and Cx43. However, it is unknown whether other factors contribute to the conduction defects observed in Irx3 knockout (Irx3(-/-)) mice. In this study, we show that during the early postnatal period, Irx3(-/-) mice develop morphological defects in the VCS which are temporally dissociated from changes in gap junction expression. These morphological defects were accompanied with progressive changes in the cardiac electrocardiogram including right bundle branch block. Hypoplastic VCS was not associated with increased apoptosis of VCS cardiomyocytes but with a lack of recruitment and maturation of ventricular cardiomyocytes into the VCS. Computational analysis followed by functional verification revealed that Irx3 promotes VCS-enriched transcripts targeted by Nkx2.5 and/or Tbx5. Altogether, these results indicate that, in addition to ensurin...Continue Reading

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Oct 5, 2016·Circulation Research·Aditi KhandekarStacey Rentschler
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Aug 27, 2021·Journal of Cardiovascular Development and Disease·Caroline ChoquetLucile Miquerol

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Datasets Mentioned

BETA
GSE21529

Methods Mentioned

BETA
transgenic
ChIP-seq
transfection
PCR

Software Mentioned

LiftOver
Expression Console
MEME
Ensembl
Affymetrix
Image J
PONEMAH Physiology Platform P3 Plus
DAVID
FIMO
Sigma Stat

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