Mouse models for cardiac conduction system development.
The mouse is the animal of choice for the study of molecular mechanisms involved in the regulation of cardiovascular morphogenesis and function. Recently, a series of genetically engineered mouse models have been reported (e.g. cGATA6/lacZ, MinK/lacZ knock-in/knock-out, engrailed2/lacZ, Cardiac troponin I/lacZ) that provide new and exciting information on the development of the atrioventricular conduction system (AVCS). On the basis of these and ongoing studies, concepts for the formation of the AVCS are continuously being adjusted. A proper understanding of the normal developmental mechanisms underlying the cardiac remodelling leading to the formation of the AVCS is imperative for the interpretation of cardiac abnormalities, including conduction disturbances, as observed in some genetically perturbed (knockout) mice. In this paper information on murine AVCS development will be integrated with published and unpublished results from studies in other vertebrates, including human and rabbit. We will illustrate that although many pieces of the puzzle still remain to be gathered, the outline of a very complex and critical event in cardiac morphogenesis is slowly emerging. Specifically, we will re-evaluate the concept of the 'primary ring' in the context of the new insights in the development of the AV junction as provided by the respective mouse models described above.