Genetic analysis of RXRα developmental function: Convergence of RXR and RAR signaling pathways in heart and eye morphogenesis

Abstract

A null mutation was generated in the mouse RXRα gene by targeted disruption. Growth deficiency occurred in heterozygote mice. Null mutants died in utero and displayed myocardial and ocular malformations. These malformations belong to the fetal vitamin A deficiency syndrome, supporting the idea that RXRα is involved in retinoid signaling in vivo. A phenotypic synergy was observed when the RXRα mutation was introduced into RARα or RARγ mutant backgrounds: RXRα null mutants and double mutants displayed similar ocular defects, which became more severe in and mutants. Furthermore, double mutants exhibited several malformations not seen in single mutants. This functional convergence strongly suggests that heterodimers mediate retinoid signaling in vivo.