Details

Autor(en) / Beteiligte

• Dyson, Emily
• Sucov, Henry M.
• Kubalak, Steven W.
• Schmid-Schonbein, Geert W.
• DeLano, Frank A.
• Evans, Donald M.
• Ross, John
• Chien, Kenneth R.

Titel

Atrial-Like Phenotype is Associated with Embryonic Ventricular Failure in Retinoid X Receptor α -/- Mice

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1995-08, Vol.92 (16), p.7386-7390

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1995

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• We have recently characterized a cardiac model of ventricular chamber defects in retinoid X receptor α (RXRα) homozygous mutant (-/-) gene-targeted mice. These mice display generalized edema, ventricular chamber hypoplasia, and muscular septal defects, and they die at embryonic day 15. To substantiate our hypothesis that the embryos are dying of cardiac pump failure, we have used digital bright-field and fluorescent video microscopy and in vivo microinjection of fluorescein-labeled albumin to analyze cardiac function. The affected embryos showed depressed ventricular function (average left ventricular area ejection fraction, 14%), ventricular septal defects, and various degrees of atrioventricular block not seen in the RXRα wild-type (+/+) and heterozygous (+/-) littermates (average left ventricular area ejection fraction, 50%). The molecular mechanisms involved in these ventricular defects were studied by evaluating expression of cardiac-specific genes known to be developmentally regulated. By in situ hybridization, aberrant, persistent expression of the atrial isoform of myosin light chain 2 was identified in the ventricles. We hypothesize that retinoic acid provides a critical signal mediated through the RXRα pathway that is required to allow progression of development of the ventricular region of the heart from its early atrial-like form to the thick-walled adult ventricle. The conduction system disturbances found in the RXRα -/- embryos may reflect a requirement of the developing conduction system for the RXRα signaling pathway, or it may be secondary to the failure of septal development.