title: Morphogenetic alterations during endocardial cushion development in the trisomy 16 (Down syndrome) mouse.
abstract: Atrioventricular septal defect occurs with a high prevalence in both human Down syndrome (trisomy 21) and the animal model for this disorder, murine trisomy 16 (Ts-16). The embryologic basis of this defect is the 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 cells and the cellular density were reduced significantly. Qualitatively, endocardial cushion shape was elongated. Immunohistochemistry revealed an apparent delay in the temporally regulated expression of cytotactin and fibronectin during cushion development. Also, anti-heparan sulfate staining was noted on newly formed cardiac mesenchymal cells. These results suggest that the failure of endocardial cushion fusion in the Ts-16 mouse may be related to an elongated shape of the cushions and an inhibition or delay in the induction, transformation, or seeding of cardiac mesenchymal cells.
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Wisconsin, Milwaukee 53201, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Hiltgen
authors.forename: R R
authors.initials: RR
authors.lastname: Markwald
authors.forename: L L
authors.initials: LL
authors.lastname: Litke
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications* / Q000196:embryology; D004694:Endocardial Cushion Defects / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006497:Heparan Sulfate / Q000378:metabolism; D007150:Immunohistochemistry; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D019063:Tenascin / Q000378:metabolism
chemical_list: D005353:Fibronectins; D006497:Heparan Sulfate; D019063:Tenascin