Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion

D Eckardt, M Theis, J Degen, T Ott, H V M van Rijen, S Kirchhoff, J-S Kim, J M T de Bakker, K Willecke

    Research output: Contribution to journalArticleAcademicpeer-review


    The gap junction protein Connexin43 (Cx43) is expressed in various cell types during embryonic development and in adult mice. Cx43 null mice (Cx43-/-) die perinatally due to cardiac malformation. In order to define the major functional role of Cx43 gap junction channels in adult mice and to circumvent perinatal death as well as direct or indirect compensation of Cx43 deficiency during development, we established a novel conditional Cx43 mouse mutant. To ablate Cx43 in adult mice in all cells that express Cx43 at a certain time, we targeted the 4-hydroxytamoxifen inducible Cre recombinase, Cre-ER(T), into the endogenous Cx43 locus. This approach left only one Cx43 coding region to be deleted upon induction of Cre-ER(T) activity. Highly efficient inducible ablation of Cx43 was shown in an embryonic stem cell test system and in adult mice. Although Cx43 protein was decreased in different tissues after induction of Cre-ER(T)-mediated recombination, cardiac abnormalities most likely account for death of those mice. Surface and telemetric ECG recordings revealed significant delay of ventricular activation and death during periods of bradyarrhythmia preceded by tachycardias. This novel approach of inducible ablation of Cx43 highlights the functional importance of normal activation of ventricular cardiomyocytes mediated by Cx43 gap junction channels in adult mouse heart to prevent initiation of fatal arrhythmias. The new mouse model should be useful for further analyses of molecular changes initiated by acute loss of Cx43 expression in various cell types.

    Original languageEnglish
    Pages (from-to)101-10
    Number of pages10
    JournalJournal of Molecular and Cellular Cardiology
    Issue number1
    Publication statusPublished - Jan 2004


    • Alleles
    • Animals
    • Bradycardia
    • Connexin 43
    • Connexins
    • Embryo, Mammalian
    • Gap Junctions
    • Gene Deletion
    • Gene Expression
    • Genes, Essential
    • Genes, Reporter
    • Integrases
    • Mice
    • Mice, Transgenic
    • Myocardium
    • Recombination, Genetic
    • Stem Cells
    • Survival Rate
    • Tamoxifen
    • Time Factors
    • Viral Proteins
    • beta-Galactosidase


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