A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels

Differentiation; Research in Biological Diversity
M FurtadoM Costa

Abstract

Nkx2-5 is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5 gene dysfunction is the most common abnormality found in patients. Here we describe a novel mouse model and subsequent implications of Nkx2-5 loss for aspects of myocardial electrical activity. In this work we have engineered a new Nkx2-5 conditional knockout mouse in which flox sites flank the entire Nkx2-5 locus, and validated this line for the study of heart development, differentiation and disease using a full deletion strategy. While our homozygous knockout mice show typical embryonic malformations previously described for the lack of the Nkx2-5 gene, hearts of heterozygous adult mice show moderate morphological and functional abnormalities that are sufficient to sustain blood supply demands under homeostatic conditions. This study further reveals intriguing aspects of Nkx2-5 function in the control of cardiac electrical activity. Using a combination of mouse genetics, biochemistry, molecular and cell biology, we d...Continue Reading

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Citations

Oct 26, 2018·Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance·Julien FrandonAlexis Jacquier
Oct 25, 2016·The Journal of Clinical Investigation·Akshay ShekharDavid S Park
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May 19, 2021·Pflügers Archiv : European journal of physiology·Wenli DaiChristopher R Weber
Jul 27, 2021·Applied Sciences·Frederick W DamenCraig J Goergen

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