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Development, Vol 124, Issue 2 313-326, Copyright © 1997 by Company of Biologists

JOURNAL ARTICLES

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

P Kastner, M Mark, N Ghyselinck, W Krezel, V Dupe, JM Grondona and P Chambon
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS-INSERM-ULP-College de France, Illkirch, France.

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.
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B Mascrez, M Mark, A Dierich, N. Ghyselinck, P Kastner, and P Chambon
The RXRalpha ligand-dependent activation function 2 (AF-2) is important for mouse development
Development, January 12, 1998; 125(23): 4691 - 4707.
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D Huang, S. Chen, A. Langston, and L. Gudas
A conserved retinoic acid responsive element in the murine Hoxb-1 gene is required for expression in the developing gut
Development, January 8, 1998; 125(16): 3235 - 3246.
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M Schubiger, A. Wade, G. Carney, J. Truman, and M Bender
Drosophila EcR-B ecdysone receptor isoforms are required for larval molting and for neuron remodeling during metamorphosis
Development, January 6, 1998; 125(11): 2053 - 2062.
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P Ruiz-Lozano, S. Smith, G Perkins, S. Kubalak, G. Boss, H. Sucov, R. Evans, and K. Chien
Energy deprivation and a deficiency in downstream metabolic target genes during the onset of embryonic heart failure in RXRalpha-/- embryos
Development, January 2, 1998; 125(3): 533 - 544.
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H. Chiba, J. Clifford, D. Metzger, and P. Chambon
Specific and Redundant Functions of Retinoid X Receptor/Retinoic Acid Receptor Heterodimers in Differentiation, Proliferation, and Apoptosis of F9 Embryonal Carcinoma Cells
J. Cell Biol., November 3, 1997; 139(3): 735 - 747.
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P Kastner, N Messaddeq, M Mark, O Wendling, J. Grondona, S Ward, N Ghyselinck, and P Chambon
Vitamin A deficiency and mutations of RXRalpha, RXRbeta and RARalpha lead to early differentiation of embryonic ventricular cardiomyocytes
Development, January 12, 1997; 124(23): 4749 - 4758.
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A. Takeshita, A. Watanabe, Y. Takada, and S. Hanazawa
Selective Stimulation by Ceramide of the Expression of the alpha Isoform of Retinoic Acid and Retinoid X Receptors in Osteoblastic Cells. A ROLE OF SPHINGOSINE 1-PHOSPHATE-MEDIATED AP-1 IN THE LIGAND-DEPENDENT TRANSCRIPTIONAL ACTIVITY OF THESE RECEPTORS
J. Biol. Chem., October 6, 2000; 275(41): 32220 - 32226.
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E. Kopf, J.-L. Plassat, V. Vivat, H. de The, P. Chambon, and C. Rochette-Egly
Dimerization with Retinoid X Receptors and Phosphorylation Modulate the Retinoic Acid-induced Degradation of Retinoic Acid Receptors alpha and gamma through the Ubiquitin-Proteasome Pathway
J. Biol. Chem., October 20, 2000; 275(43): 33280 - 33288.
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D. L. Misner, S. Jacobs, Y. Shimizu, A. M. de Urquiza, L. Solomin, T. Perlmann, L. M. De Luca, C. F. Stevens, and R. M. Evans
Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity
PNAS, September 25, 2001; 98(20): 11714 - 11719.
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