MORPHOGENETIC ALTERATIONS DURING ENDOCARDIAL CUSHION DEVELOPMENT IN THE TRISOMY-16 (DOWN-SYNDROME) MOUSE

Atrioventricular septal defect occurs with a high prevalence in both h uman Down syndrome (trisomy 21) and the animal model for this disorder , murine trisomy 16 (Ts-16). The embryologic basis of this defect is t he failure of the endocardial cushions to fuse. Quantitatively, Ts-16 hearts, when compared to normal mouse embryos, were not significantly different in either the estimates of whole heart volume or endocardial cushion volume. However, both the raw number of cardiac mesenchyme ce lls and the cellular density were reduced significantly. Qualitatively , endocardial cushion shape was elongated. Immunohistochemistry reveal ed an apparent delay in the temporally regulated expression of cytotac tin and fibronectin during cushion development. Also, anti-heparan sul fate staining was noted on newly formed cardiac mesenchymal cells. The se results suggest that the failure of endocardial cushion fusion in t he Ts-16 mouse may be related to an elongated shape of the cushions an d an inhibition or delay in the induction, transformation, or seeding of cardiac mesenchymal cells.