Tamoxifen-inducible gene deletion in the cardiac conduction system
| Autor: | Stefan Herrmann, Robert Feil, Andreas Ludwig, Juliane Stieber, Franz Hofmann, Susanne Feil, Evelyn Hoesl, Elisabeth Tybl |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_treatment
Transgene Quantitative Trait Loci Cre recombinase Cyclic Nucleotide-Gated Cation Channels Mice Transgenic Biology Cardiac pacemaker Mice Heart Conduction System Heart rate medicine Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Animals Molecular Biology Recombination Genetic Integrases Sinoatrial node Estrogen Antagonists Atrioventricular node Molecular biology Cell biology Tamoxifen medicine.anatomical_structure Electrical conduction system of the heart Cardiology and Cardiovascular Medicine Gene Deletion medicine.drug |
| Zdroj: | Journal of molecular and cellular cardiology. 45(1) |
| ISSN: | 1095-8584 |
| Popis: | Temporally controlled gene deletion provides a powerful technique for examination of gene function in vivo. To permit use of this technology in the study of cardiac pacemaking, we attempted to generate a mouse line expressing an inducible Cre recombinase selectively in cardiac pacemaker cells. The tamoxifen-inducible CreER(T2) construct was 'knocked in' into the pacemaker channel HCN4 locus. In the absence of inducing agent, recombination was undetectable in HCN4-KiT mice. After injection of tamoxifen, highly selective and efficient recombination was observed in the sinoatrial and atrioventricular node. Expression of Cre and tamoxifen per se did not affect cardiac rhythm, basal heart rate and heart rate modulation. By crossing these animals with floxed HCN4 mice, complete deletion of this gene in the sinoatrial node could be achieved. HCN4-KiT mice represent the first tool for the temporally controlled inactivation of floxed target genes selectively in the conduction system of the murine heart. |
| Databáze: | OpenAIRE |
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