Phenotypically silent Cre recombination within the postnatal ventricular conduction system

Samadrita Bhattacharyya, Minoti Bhakta, Nikhil Vilas Munshi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The cardiac conduction system (CCS) is composed of specialized cardiomyocytes that initiate and maintain cardiac rhythm. Any perturbation to the normal sequence of electrical events within the heart can result in cardiac arrhythmias. To understand how cardiac rhythm is established at the molecular level, several genetically modified mouse lines expressing Cre recombinase within specific CCS compartments have been created. In general, Cre driver lines have been generated either by homologous recombination of Cre into an endogenous locus or Cre expression driven by a randomly inserted transgene. However, haploinsufficiency of the endogenous gene compromises the former approach, while position effects negatively impact the latter. To address these limitations, we generated a Cre driver line for the ventricular conduction system (VCS) that preserves endogenous gene expression by targeting the Contactin2 (Cntn2) 3' untranslated region (3'UTR). Here we show that Cntn23'UTR-IRES-Cre-EGFP/+ mice recombine floxed alleles within the VCS and that Cre expression faithfully recapitulates the spatial distribution of Cntn2 within the heart. We further demonstrate that Cre expression initiates after birth with preservation of native Cntn2 protein. Finally, we show that Cntn23'UTR-IRES-Cre-EGFP/+ mice maintain normal cardiac mechanical and electrical function. Taken together, our results establish a novel VCS-specific Cre driver line without the adverse consequences of haploinsufficiency or position effects. We expect that our new mouse line will add to the accumulating toolkit of CCS-specific mouse reagents and aid characterization of the cell-autonomous molecular circuitry that drives VCS maintenance and function.

Original languageEnglish (US)
Article numbere0174517
JournalPLoS One
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2017

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Untranslated Regions
Genetic Recombination
mice
position effect (genetics)
3' Untranslated Regions
Haploinsufficiency
Gene expression
Spatial distribution
Genes
heart
Gene Targeting
Homologous Recombination
homologous recombination
arrhythmia
3' untranslated regions
Proteins
Transgenes
Cardiac Myocytes
transgenes
preserves

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Phenotypically silent Cre recombination within the postnatal ventricular conduction system. / Bhattacharyya, Samadrita; Bhakta, Minoti; Vilas Munshi, Nikhil.

In: PLoS One, Vol. 12, No. 3, e0174517, 01.03.2017.

Research output: Contribution to journalArticle

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