FUNCTION OF RETINOIC ACID RECEPTOR-GAMMA IN THE MOUSE

Null mutant mice for retinoic acid receptor gamma2 (RARgamma2) or all RARgamma isoforms were generated. RARgamma2 mutants appeared normal, whereas RARgamma 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 RARgamma 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 RARgamma. The observed RARgamma 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.