The specialized myocytes of the ventricular conduction system (VCS) coordinate ventricular contraction and are critical for efficient pumping by the heart. Impaired VCS conduction is characteristic of inherited forms of cardiac conduction disorders. Here we show that the Iroquois homeobox 3 (Irx3) transcription factor is preferentially expressed in the developing and mature VCS. Loss of Irx3 in mice results in slowed VCS conduction and prolonged QRS duration with right bundle branch block, caused by reduction (42%) in VCS-specific connexin 40 (Cx40) expression and VCS fiber hypoplasia, absent in littermate controls. Therefore, we show that the role of Irx3 in the heart is two-fold, whereby Irx3 (1) indirectly regulates Cx40 gene expression, by repressing a repressor of Cx40 transcript, and (2) controls VCS maturation, possibly in an Nkx2-5-dependent manner. To our knowledge, this is the first report of a role for Irx3 in regulating the development and function of the VCS.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/30140 |
| Date | 30 November 2011 |
| Creators | Rosen, Anna |
| Contributors | Backx, Peter |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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