Function of Retinoic Acid Receptor Gamma in the Mouse

Cell. 1993 May 21;73(4):643-58. doi: 10.1016/0092-8674(93)90246-m.

Abstract

Null mutant mice for retinoic acid receptor gamma 2 (RAR gamma 2) or all RAR gamma isoforms were generated. RAR gamma 2 mutants appeared normal, whereas RAR gamma mutants exhibited growth deficiency, early lethality, and male sterility due to squamous metaplasia of the seminal vesicles and prostate. These defects were previously observed in vitamin A-deficient animals and could be prevented by RA administration, demonstrating that RAR gamma mediates some of the retinoid signal in vivo. Congenital defects included Harderian gland agenesis, tracheal cartilage malformations, and homeotic transformations along the rostral axial skeleton, establishing a direct link between RA and patterning of the axial skeleton. We also show that in utero RA-induced lumbosacral truncations are mediated by RAR gamma. The observed RAR gamma null phenotype suggests a high degree of functional redundancy among the RARs. The variable penetrance of some of the observed defects is discussed in light of this redundancy and stochastic variation of gene activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Animals
  • Base Sequence
  • Bone and Bones / abnormalities
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cartilage / abnormalities
  • Embryonic and Fetal Development / genetics*
  • Female
  • Genes, Lethal
  • Growth Disorders / etiology
  • Growth Disorders / genetics
  • Homozygote
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Receptors, Retinoic Acid
  • Recombination, Genetic
  • Tretinoin / pharmacology
  • Vitamin A Deficiency / complications

Substances

  • Carrier Proteins
  • Receptors, Retinoic Acid
  • Tretinoin