Résumé :
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Communication n° 239. In humans, mutations affecting cardiac genes have been shown to modify the function of the cardiac conduction system (CCS). The CCS is a prerequisite for the synchronisation of the heart beats and its localization within the adult myocardium is well established. However, the molecular mechanisms responsible for its differentiation and development are not understood. The aim of this study is to get insights into the genetic and epigenetic factors that control the development and differentiation of the CCS. We have generated a T3.1 transgenic mouse line which traces out components of the CCS throughout cardiac development and adulthood. Breeding the T3.1 and Cx40+/EGFP mouse lines we demonstrate that distribution of LacZ in the T3.1 line is similar to the expression pattern described for the Cx40+/EGFP in the adult CCS. In addition, beta-galactosidase activity was detected in the atrial cardiomyocytes, the epicardium and the AV valves. In the embryonic heart, the expression of the LacZ reporter gene was shown to follow the expression of the Cx40 gene. However, ectopic sites of expression were also observed. At the early stage of cardiogenesis LacZ positive cells were shown to distribute at the position of the primitive CCS (first identified with the GlN2 marker in the human embryonic heart). Latter, the distribution of the cells reproduces the development of the primitive rings devoid of Cx40 expression. Endothelin and neuregulin-1 used in in vitro culture assays were not sufficient to increase the number of reporter gene expressing cells. In summary the T3.1 mouse line provides a useful model for understanding the development of the CCS and revealing the transcriptional differences between different heart regions.
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