Genetic evidence that the retinoid signal is transduced by heterodimeric RXR/RAR functional units during mouse development.

Fiche publication


Date publication

janvier 1997

Journal

Development (Cambridge, England)

Auteurs

Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr KASTNER Philippe, Dr GHYSELINCK Norbert, Dr MARK Manuel, Dr KREZEL Wojciech


Tous les auteurs :
Kastner P, Mark M, Ghyselinck N, Krezel W, Dupé V, Grondona JM, Chambon P

Résumé

We describe here the analysis of congenital malformations in compound mutant fetuses bearing null alleles in one RXR (alpha, beta or gamma) and one RAR (alpha, beta or gamma) isotype gene. A marked synergy was observed between the effects of mutations in RXR alpha and RARs, as a large number of developmental defects previously found mainly in RAR single and compound mutants were recapitulated in specific RXR alpha/RAR compound mutants. Several malformations were seen only in one type of RXR alpha/RAR mutant combination, whereas others were seen in several types of RXR alpha/RAR double mutants. No synergy was observed between the effects of mutations of either RXR beta or RXR gamma mutations and those of any of the RAR mutations. These genetic data suggest that RXR/RAR heterodimers are the functional units transducing the retinoid signal for a large number of RA-dependent processes, and furthermore, that RXR alpha is the main RXR implicated in the developmental functions of RARs. The significance of these observations is discussed with respect to the problem of functional specificity and redundancy among retinoid receptors in vivo.

Mots clés

Abnormalities, Multiple, embryology, Animals, Chromosome Mapping, Dimerization, Gene Expression Regulation, Developmental, Mice, Mice, Mutant Strains, Receptors, Retinoic Acid, biosynthesis, Retinoic Acid Receptor alpha, Retinoid X Receptors, Signal Transduction, Transcription Factors, biosynthesis

Référence

Development. 1997 Jan;124(2):313-26