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Morphogenetic alterations during endocardial cushion development in the trisomy 16 (Down syndrome) mouse
G G Hiltgen1, R R Markwald, L L Litke
1Department of Cellular Biology and Anatomy, Medical College of Wisconsin, Milwaukee 53201, USA.
Pediatric Cardiology
|January 1, 1996
Summary
Down syndrome is linked to heart defects like atrioventricular septal defects. In Ts-16 mice, reduced cardiac mesenchyme cells and altered cushion shape may cause fusion failure.
Area of Science:
- Developmental Biology
- Cardiovascular Science
- Genetics
Background:
- Atrioventricular septal defects (AVSD) are common in Down syndrome (DS) and its mouse model, trisomy 16 (Ts-16).
- AVSD results from failed endocardial cushion fusion during heart development.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying endocardial cushion fusion defects in Ts-16 mouse embryos.
- To compare cardiac development in Ts-16 and normal mouse embryos.
Main Methods:
- Quantitative analysis of heart and endocardial cushion volumes.
- Assessment of cardiac mesenchyme cell number and density.
- Immunohistochemical analysis of extracellular matrix proteins (cytotactin, fibronectin) and heparan sulfate.
- Qualitative evaluation of endocardial cushion morphology.
Main Results:
- Ts-16 hearts showed no significant difference in total volume or endocardial cushion volume compared to controls.
- A significant reduction in cardiac mesenchyme cell number and density was observed in Ts-16 embryos.
- Endocardial cushions in Ts-16 embryos exhibited an elongated shape.
- Delayed expression of cytotactin and fibronectin, and presence of anti-heparan sulfate staining on mesenchymal cells were noted.
Conclusions:
- The failure of endocardial cushion fusion in Ts-16 mice may stem from an elongated cushion shape.
- Inhibition or delay in cardiac mesenchyme cell induction, transformation, or seeding is implicated in the observed defects.