Fiche publication
Date publication
juin 2001
Journal
Development (Cambridge, England)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
,
Dr MARK Manuel
,
Dr KREZEL Wojciech
Tous les auteurs :
Mascrez B, Mark M, Krezel W, Dupé V, LeMeur M, Ghyselinck NB, Chambon P
Lien Pubmed
Résumé
We have engineered a mouse mutation that specifically deletes most of the RXR alpha N-terminal A/B region, which includes the activation function AF-1 and several phosphorylation sites. The homozygous mutants (RXR alpha af1(o)), as well as compound mutants that further lack RXR beta and RXR gamma, are viable and display a subset of the abnormalities previously described in RXR alpha-null mutants. In contrast, RXR alpha af1(o)/RAR(-/-)(alpha, beta or gamma) compound mutants die in utero and exhibit a large array of malformations that nearly recapitulate the full spectrum of the defects that characterize the fetal vitamin A-deficiency (VAD) syndrome. Altogether, these observations indicate that the RXR alpha AF-1 region A/B is functionally important, although less so than the ligand-dependent activation function AF-2, for efficiently transducing the retinoid signal through RAR/RXR alpha heterodimers during embryonic development. Moreover, it has a unique role in retinoic acid-dependent involution of the interdigital mesenchyme. During early placentogenesis, both the AF-1 and AF-2 activities of RXR alpha, beta and gamma appear to be dispensable, suggesting that RXRs act as silent heterodimeric partners in this process. However, AF-2 of RXR alpha, but not AF-1, is required for differentiation of labyrinthine trophoblast cells, a late step in the formation of the placental barrier.
Mots clés
Amino Acid Sequence, Animals, Base Sequence, Gene Targeting, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Mutagenesis, Promoter Regions, Genetic, Receptors, Retinoic Acid, genetics, Retinoid X Receptors, Trans-Activators, genetics, Transcription Factors, genetics
Référence
Development. 2001 Jun;128(11):2049-62
