Genetic analysis of RXR alpha developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis

Cell. 1994 Sep 23;78(6):987-1003. doi: 10.1016/0092-8674(94)90274-7.


A null mutation was generated in the mouse RXR alpha 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 RXR alpha is involved in retinoid signaling in vivo. A phenotypic synergy was observed when the RXR alpha mutation was introduced into RAR alpha or RAR gamma mutant backgrounds: RXR alpha null mutants and RXR alpha +/-/RAR gamma-/- double mutants displayed similar ocular defects, which became more severe in RXR alpha-/-/RAR gamma+/- and RXR alpha-/-/RAR gamma-/- mutants. Furthermore, RXR alpha/RAR double mutants exhibited several malformations not seen in single mutants. This functional convergence strongly suggests that RXR alpha/RAR heterodimers mediate retinoid signaling in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / abnormalities
  • Aorta, Thoracic / embryology
  • Cell Differentiation
  • Cell Division
  • Eye / embryology*
  • Eye Abnormalities / genetics
  • Genes, Lethal / genetics
  • Heart / embryology*
  • Heart Defects, Congenital / genetics
  • Image Processing, Computer-Assisted
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Mutation
  • Myocardium / cytology
  • Myocardium / ultrastructure
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Retinoic Acid / deficiency
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Retinoic Acid / physiology*
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Signal Transduction*
  • Transcription Factors*


  • Rara protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Transcription Factors
  • retinoic acid receptor beta
  • retinoic acid receptor gamma