spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mascrez, B.
Right arrow Articles by Chambon, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mascrez, B.
Right arrow Articles by Chambon, P.
Development 128, 2049-2062 (2001)
© 2001 The Company of Biologists Limited

Differential contributions of AF-1 and AF-2 activities to the developmental functions of RXR{alpha}

Bénédicte Mascrez, Manuel Mark, Wojciech Krezel, Valérie Dupé, Marianne LeMeur, Norbert B. Ghyselinck and Pierre Chambon*

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP-Collège de France, BP163, 67404 Illkirch Cedex, C.U. de Strasbourg, France

*Author for correspondence (e-mail: chambon{at}igbmc.u-strasbg.fr)

Accepted March 8, 2001

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}af1o), as well as compound mutants that further lack RXRß and RXR{gamma}, are viable and display a subset of the abnormalities previously described in RXR{alpha}-null mutants. In contrast, RXR{alpha}af1o/RAR-/-({alpha}, ß 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}, ß 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.

Key words: Nuclear receptor, Retinoic acid, Gene knockout, Transcriptional activity, Activation function, Placenta, Limb, Mouse




This article has been cited by other articles:


Home page
 J. Immunol.Home page
H.-C. Lee, M. B. Headley, M. Iseki, K. Ikuta, and S. F. Ziegler
Cutting Edge: Inhibition of NF-{kappa}B-Mediated TSLP Expression by Retinoid X Receptor
J. Immunol., October 15, 2008; 181(8): 5189 - 5193.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
P. Germain, P. Chambon, G. Eichele, R. M. Evans, M. A. Lazar, M. Leid, A. R. De Lera, R. Lotan, D. J. Mangelsdorf, and H. Gronemeyer
International Union of Pharmacology. LXIII. Retinoid X Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 760 - 772.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
Genetically Modified Animals in Endocrinology
Endocr. Rev., December 1, 2005; 26(7): 985 - 993.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. Chen, S. Beaven, and P. Tontonoz
Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha
J. Lipid Res., December 1, 2005; 46(12): 2570 - 2579.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
T. Nakanishi, J.-i. Nishikawa, Y. Hiromori, H. Yokoyama, M. Koyanagi, S. Takasuga, J.-i. Ishizaki, M. Watanabe, S.-i. Isa, N. Utoguchi, et al.
Trialkyltin Compounds Bind Retinoid X Receptor to Alter Human Placental Endocrine Functions
Mol. Endocrinol., October 1, 2005; 19(10): 2502 - 2516.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
P. Chambon
The Nuclear Receptor Superfamily: A Personal Retrospect on the First Two Decades
Mol. Endocrinol., June 1, 2005; 19(6): 1418 - 1428.
[Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 DevelopmentHome page
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]

Home page
 DevelopmentHome page
L. Cherbas, X. Hu, I. Zhimulev, E. Belyaeva, and P. Cherbas
EcR isoforms in Drosophila: testing tissue-specific requirements by targeted blockade and rescue
Development, March 2, 2003; 130(2): 271 - 284.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Desclozeaux, I. N. Krylova, F. Horn, R. J. Fletterick, and H. A. Ingraham
Phosphorylation and Intramolecular Stabilization of the Ligand Binding Domain in the Nuclear Receptor Steroidogenic Factor 1
Mol. Cell. Biol., October 15, 2002; 22(20): 7193 - 7203.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Bastien, S. Adam-Stitah, J.-L. Plassat, P. Chambon, and C. Rochette-Egly
The Phosphorylation Site Located in the A Region of Retinoic X Receptor alpha Is Required for the Antiproliferative Effect of Retinoic Acid (RA) and the Activation of RA Target Genes in F9 Cells
J. Biol. Chem., August 2, 2002; 277(32): 28683 - 28689.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2001