The mouse with trisomy 16 as a model of human hearts with common atrioventricular junction

OBJECTIVE: To establish if the mouse with trisomy 16 is a suitable animal model with which to elucidate the development of a common atrioventricular junction. METHODS: The junctional morphologies in the normal human heart and those with a common atrioventricular junction are compared and contrasted. These are then related to observations made in normal mice and those with trisomy 16. So as better to understand development, a full description is given first of the normal atrioventricular junctions. Developmental implications are discussed because failure of fusion of the endocardial cushions cannot account for all the anomalies found in RXR alpha knockout, and in iv/iv mice. RESULTS: Mice with trisomy 16 showed evidence of deficiencies of atrioventricular septation and possessed a common atrioventricular junction, but the valvar orifices were not balanced between the ventricles as is the case in humans. Whilst some mice showed affinities with human tricuspid atresia, other cardiac malformations in the mice had no counterparts in human cardiac pathology. In humans both "partial" and "complete" forms of "atrioventricular canal malformations" share a basically common muscular junctional morphology, the differences being due exclusively to the way the bridging leaflets are fused to each other and/or the septum. CONCLUSIONS: It is simplistic to use the mouse with trisomy 16 as a model for cardiac abnormalities seen in humans. A spectrum more comparable to humans is found in RXR knockout mice. Study of the iv/iv mouse may help elucidate the genetic steps involved in normal and abnormal atrioventricular septation.