|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 125, Issue 23 4691-4707, Copyright © 1998 by Company of Biologists
JOURNAL ARTICLES |
B Mascrez, M Mark, A Dierich, NB Ghyselinck, P Kastner and P Chambon
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS-INSERM-ULP-College de France, BP163, CU de Strasbourg, France.
We have engineered a mouse mutation that specifically deletes the C-terminal 18 amino acid sequence of the RXRalpha protein. This deletion corresponds to the last helical alpha structure (H12) of the ligand-binding domain (LBD), and includes the core of the Activating Domain of the Activation Function 2 (AF-2 AD core) that is thought to be crucial in mediating ligand-dependent transactivation by RXRalpha. The homozygous mutants (RXRalpha af2(o)), which die during the late fetal period or at birth, exhibit a subset of the abnormalities previously observed in RXRalpha -/- mutants, often with incomplete penetrance. In marked contrast, RXRalpha af2(o)/RXRbeta -/- and RXRalpha af2(o)/RXRbeta -/- /RXRgamma -/- compound mutants display a large array of malformations, which nearly recapitulate the full spectrum of the defects that characterize the fetal vitamin A-deficiency (VAD) syndrome and were previously found in RAR single and compound mutants, as well as in RXRalpha/RAR(alpha, beta or gamma) compound mutants. Analysis of RXRalpha af2(o)/RAR(alpha, beta or gamma) compound mutants also revealed that they exhibit many of the defects observed in the corresponding RXR alpha/RAR compound mutants. Together, these results demonstrate the importance of the integrity of RXR AF-2 for the developmental functions mediated by RAR/RXR heterodimers, and hence suggest that RXR ligand-dependent transactivation is instrumental in retinoid signalling during development.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Mascrez, N. B. Ghyselinck, P. Chambon, and M. Mark A transcriptionally silent RXR{alpha} supports early embryonic morphogenesis and heart development PNAS, March 17, 2009; 106(11): 4272 - 4277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Vernet, C. Dennefeld, M. Klopfenstein, A. Ruiz, D. Bok, N. B Ghyselinck, and M. Mark Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation Reproduction, November 1, 2008; 136(5): 619 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Calleja, N. Messaddeq, B. Chapellier, H. Yang, W. Krezel, M. Li, D. Metzger, B. Mascrez, K. Ohta, H. Kagechika, et al. Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes Genes & Dev., June 1, 2006; 20(11): 1525 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Genetically Modified Animals in Endocrinology Endocr. Rev., December 1, 2005; 26(7): 985 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Matt, V. Dupe, J.-M. Garnier, C. Dennefeld, P. Chambon, M. Mark, and N. B. Ghyselinck Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells Development, November 1, 2005; 132(21): 4789 - 4800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Li, N. Messaddeq, M. Teletin, J.-L. Pasquali, D. Metzger, and P. Chambon Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin PNAS, October 11, 2005; 102(41): 14795 - 14800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Xu, F. Guidez, A. Glasow, D. Chung, K. Petrie, K. Stegmaier, K.-K. Wang, J. Zhang, Y. Jing, A. Zelent, et al. Benzodithiophenes Potentiate Differentiation of Acute Promyelocytic Leukemia Cells by Lowering the Threshold for Ligand-Mediated Corepressor/Coactivator Exchange with Retinoic Acid Receptor {alpha} and Enhancing Changes in all-trans-Retinoic Acid-Regulated Gene Expression Cancer Res., September 1, 2005; 65(17): 7856 - 7865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Serpente, S. Tumpel, N. B. Ghyselinck, K. Niederreither, L. M. Wiedemann, P. Dolle, P. Chambon, R. Krumlauf, and A. P. Gould Direct crossregulation between retinoic acid receptor {beta} and Hox genes during hindbrain segmentation Development, February 1, 2005; 132(3): 503 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takiyama, N. Miyokawa, A. Sugawara, S. Kato, K. Ito, K. Sato, K. Oikawa, H. Kobayashi, S. Kimura, and M. Tateno Decreased Expression of Retinoid X Receptor Isoforms in Human Thyroid Carcinomas J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5851 - 5861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lengqvist, A. Mata de Urquiza, A.-C. Bergman, T. M. Willson, J. Sjovall, T. Perlmann, and W. J. Griffiths Polyunsaturated Fatty Acids Including Docosahexaenoic and Arachidonic Acid Bind to the Retinoid X Receptor {alpha} Ligand-binding Domain Mol. Cell. Proteomics, July 1, 2004; 3(7): 692 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Luria and J. D. Furlow Spatiotemporal retinoid-X receptor activation detected in live vertebrate embryos PNAS, June 15, 2004; 101(24): 8987 - 8992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mori, D. Metzger, S. Picaud, C. Hindelang, M. Simonutti, J. Sahel, P. Chambon, and M. Mark Retinal Dystrophy Resulting from Ablation of RXR{alpha} in the Mouse Retinal Pigment Epithelium Am. J. Pathol., February 1, 2004; 164(2): 701 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wallen-Mackenzie, A. M. de Urquiza, S. Petersson, F. J. Rodriguez, S. Friling, J. Wagner, P. Ordentlich, J. Lengqvist, R. A. Heyman, E. Arenas, et al. Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells Genes & Dev., December 15, 2003; 17(24): 3036 - 3047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Dupe, N. Matt, J.-M. Garnier, P. Chambon, M. Mark, and N. B. Ghyselinck A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment PNAS, November 25, 2003; 100(24): 14036 - 14041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Mic, A. Molotkov, D. M. Benbrook, and G. Duester Retinoid activation of retinoic acid receptor but not retinoid X receptor is sufficient to rescue lethal defect in retinoic acid synthesis PNAS, June 10, 2003; 100(12): 7135 - 7140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Matt, N. B. Ghyselinck, O. Wendling, P. Chambon, and M. Mark Retinoic acid-induced developmental defects are mediated by RAR{beta}/RXR heterodimers in the pharyngeal endoderm Development, May 15, 2003; 130(10): 2083 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Clabby, T. A. Robison, H. F. Quigley, D. B. Wilson, and D. P. Kelly Retinoid X Receptor alpha Represses GATA-4-mediated Transcription via a Retinoid-dependent Interaction with the Cardiac-enriched Repressor FOG-2 J. Biol. Chem., February 14, 2003; 278(8): 5760 - 5767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Weber, M. Schuler, C. Gerard, M. Mark, D. Metzger, and P. Chambon Temporally Controlled Site-Specific Mutagenesis in the Germ Cell Lineage of the Mouse Testis Biol Reprod, February 1, 2003; 68(2): 553 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M MADEN Vitamin A and the developing embryo Postgrad. Med. J., August 1, 2001; 77(910): 489 - 491. [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Benoit, M. Flexor, F. Besancon, L. Altucci, A. Rossin, J. Hillion, Z. Balajthy, L. Legres, E. Segal-Bendirdjian, H. Gronemeyer, et al. Autonomous Rexinoid Death Signaling Is Suppressed by Converging Signaling Pathways in Immature Leukemia Cells Mol. Endocrinol., July 1, 2001; 15(7): 1154 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Wendling, N. B. Ghyselinck, P. Chambon, and M. Mark Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterning Development, June 1, 2001; 128(11): 2031 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mori, N. B. Ghyselinck, P. Chambon, and M. Mark Systematic Immunolocalization of Retinoid Receptors in Developing and Adult Mouse Eyes Invest. Ophthalmol. Vis. Sci., May 1, 2001; 42(6): 1312 - 1318. [Abstract] [Full Text]
|
|
|
|
|
|
S. Abu-Abed, P. Dollé, D. Metzger, B. Beckett, P. Chambon, and M. Petkovich The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures Genes & Dev., January 15, 2001; 15(2): 226 - 240. [Abstract] [Full Text]
|
|
|
|
|
|
K Niederreither, J Vermot, N Messaddeq, B Schuhbaur, P Chambon, and P Dolle Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse Development, January 4, 2001; 128(7): 1019 - 1031. [Abstract] [PDF]
|
|
|
|
|
|
M Li, H Chiba, X Warot, N Messaddeq, C Gerard, P Chambon, and D Metzger RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations Development, January 3, 2001; 128(5): 675 - 688. [Abstract] [PDF]
|
|
|
|
 |
|
 A. M. d. Urquiza, S. Liu, M. Sjöberg, R. H. Zetterström, W. Griffiths, J. Sjövall, and T. Perlmann Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain Science, December 15, 2000; 290(5499): 2140 - 2144. [Abstract] [Full Text]
|
|
|
|
 |
|
 A Parlesak, I Menzl, A Feuchter, J C Bode, and C Bode Inhibition of retinol oxidation by ethanol in the rat liver and colon Gut, December 1, 2000; 47(6): 825 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Weston, V. Rosen, R. A.S. Chandraratna, and T. M. Underhill Regulation of Skeletal Progenitor Differentiation by the Bmp and Retinoid Signaling Pathways J. Cell Biol., February 21, 2000; 148(4): 679 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Plassat, L Penna, P Chambon, and C Rochette-Egly The conserved amphipatic alpha-helical core motif of RARgamma and RARalpha activating domains is indispensable for RA-induced differentiation of F9 cells J. Cell Sci., January 8, 2000; 113(16): 2887 - 2895. [Abstract] [PDF]
|
|
|
|
|
|
O Wendling, C Dennefeld, P Chambon, and M Mark Retinoid signaling is essential for patterning the endoderm of the third and fourth pharyngeal arches Development, January 4, 2000; 127(8): 1553 - 1562. [Abstract] [PDF]
|
|
|
|
|
|
B. Desvergne and W. Wahli Peroxisome Proliferator-Activated Receptors: Nuclear Control of Metabolism Endocr. Rev., October 1, 1999; 20(5): 649 - 688. [Abstract] [Full Text]
|
|
|
|
|
|
S. Adam-Stitah, L. Penna, P. Chambon, and C. Rochette-Egly Hyperphosphorylation of the Retinoid X Receptor alpha by Activated c-Jun NH2-terminal Kinases J. Biol. Chem., July 2, 1999; 274(27): 18932 - 18941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Dilworth, C. Fromental-Ramain, E. Remboutsika, A. Benecke, and P. Chambon Ligand-dependent activation of transcription in vitro by retinoic acid receptor alpha /retinoid X receptor alpha heterodimers that mimics transactivation by retinoids in vivo PNAS, March 2, 1999; 96(5): 1995 - 2000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Wendling, P. Chambon, and M. Mark Retinoid X receptors are essential for early mouse development and placentogenesis PNAS, January 19, 1999; 96(2): 547 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Dupe, N. Ghyselinck, O Wendling, P Chambon, and M Mark Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse Development, January 11, 1999; 126(22): 5051 - 5059. [Abstract] [PDF]
|
|
|
|
|
|
T. Imai, M. Jiang, P. Chambon, and D. Metzger Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes PNAS, January 2, 2001; 98(1): 224 - 228. [Abstract] [Full Text] [PDF]
|
|
