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Related Experiment Videos

Phenotypically silent Cre recombination within the postnatal ventricular conduction system.

Samadrita Bhattacharyya1, Minoti Bhakta1, Nikhil Vilas Munshi1,2,3,4

  • 1Department of Internal Medicine (Cardiology Division), UT Southwestern Medical Center, Dallas, TX, United States of America.

Plos One
|March 31, 2017
PubMed
Summary

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Researchers developed a new mouse model for studying the heart's electrical system. This novel tool, targeting the ventricular conduction system (VCS), avoids common genetic engineering issues, enabling better research into cardiac rhythm.

Area of Science:

  • Cardiovascular Biology
  • Genetics
  • Molecular Biology

Background:

  • The cardiac conduction system (CCS) generates and maintains heart rhythm; disruptions cause arrhythmias.
  • Existing Cre driver mouse lines for CCS research have limitations like haploinsufficiency or position effects.
  • Understanding CCS molecular mechanisms requires precise genetic tools.

Purpose of the Study:

  • To create a novel Cre driver mouse line for the ventricular conduction system (VCS).
  • To overcome limitations of existing methods, ensuring preservation of endogenous gene expression and avoiding position effects.
  • To provide a reliable tool for studying VCS maintenance and function.

Main Methods:

  • Generated a Cre driver line targeting the Contactin2 (Cntn2) 3' untranslated region (3'UTR).

Related Experiment Videos

  • Utilized homologous recombination to insert Cre-IRES-EGFP into the Cntn2 locus.
  • Validated recombination specificity, Cre expression timing, and impact on native Cntn2 protein levels.

    • Main Results:

    • Cntn23'UTR-IRES-Cre-EGFP/+ mice show specific recombination within the VCS.
    • Cre expression is initiated postnatally and preserves endogenous Cntn2 protein.
    • These mice exhibit normal cardiac mechanical and electrical function, indicating no adverse effects.

    Conclusions:

    • Established a novel, VCS-specific Cre driver line (Cntn23'UTR-IRES-Cre-EGFP/+) without haploinsufficiency or position effects.
    • This new tool facilitates the study of cell-autonomous molecular circuitry in VCS.
    • The mouse line expands the toolkit for cardiac conduction system research.