1. Compartment-Selective Sensitivity of Cardiovascular Morphogenesis to Combinations of Retinoic Acid Receptor Gene Mutations
- Author
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Jiangming Luo, Ronald M. Evans, Robin Y. Lee, Vincent Giguère, and Henry M. Sucov
- Subjects
Heart Defects, Congenital ,medicine.medical_specialty ,Receptors, Retinoic Acid ,Physiology ,Coronary Vessel Anomalies ,Retinoic acid ,Persistent truncus arteriosus ,Aorta, Thoracic ,Gene mutation ,Retinoid X receptor ,Biology ,medicine.disease_cause ,Cardiovascular System ,Bulbus cordis ,Veins ,Embryonic and Fetal Development ,Mice ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Receptor ,Aorta ,Mutation ,Heart ,medicine.disease ,Heart Valves ,Mice, Mutant Strains ,Retinoic acid receptor ,Endocrinology ,chemistry ,cardiovascular system ,Cancer research ,Cardiology and Cardiovascular Medicine - Abstract
Abstract Several aspects of normal cardiovascular development require signaling by the vitamin A metabolite retinoic acid. We have previously established germ-line mutations in mice in the genes that encode the RARα1, RARβ, and RXRα retinoic acid receptors as a means of studying the function of these receptors in vivo. Although mutation of RXRα results in fetal ventricular defects, the RARα1 and RARβ mutations are apparently nonphenotypic in the heart and elsewhere. In this study, we have established and analyzed combinations of these receptor gene mutations. Malformations of the ventricular chamber (chamber hypoplasia and muscular ventricular septal defects), conotruncus (double-outlet right ventricle, transposition, and membranous ventricular septal defects), aortic sac (persistent truncus arteriosus and aorticopulmonary window), and aortic arch–derived arteries were recovered in various combinations of the RARα1, RARβ, and RXRα gene mutations. Depending on the combination of receptor mutations, selective defects were obtained in specific cardiovascular compartments, suggestive of differential expression or function of each receptor within domains of the developing heart.
- Published
- 1997