spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Full Text (PDF)
Right arrow References
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 Sucov, H. M.
Right arrow Articles by Evans, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sucov, H. M.
Right arrow Articles by Evans, R. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Development, Vol 121, Issue 12 3997-4003, Copyright © 1995 by Company of Biologists

JOURNAL ARTICLES

Mouse embryos lacking RXR alpha are resistant to retinoic-acid-induced limb defects

HM Sucov, JC Izpisua-Belmonte, Y Ganan and RM Evans
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Embryonic exposure to the vitamin A metabolite retinoic acid (RA) causes malformations in numerous developing tissues, including the limbs, which serves as a model system of retinoic acid action. RA treatment of wild-type mouse embryos results in digit truncations and long bone reductions. These effects are mediated by products of the retinoic acid and retinoid X receptor genes (RARs and RXRs), members of the nuclear receptor family of ligand-dependent transcription factors. Mouse embryos homozygous for a mutation in the RXR alpha gene appear normal in limb development, although such embryos are phenotypically affected in other tissues. We now describe resistance to limb malformations normally induced by teratogenic RA exposure in the RXR alpha-/- background. RA treatments that cause limb defects in 100% of wild-type embryos fail to elicit malformations in RXR alpha homozygotes, implicating RXR alpha as a component in the teratogenic process in the limbs. Heterozygous embryos are intermediate in sensitivity to RA, suggesting the importance of RXR alpha gene dosage in limb teratogenesis. Expression of the RA-inducible gene RAR beta 2 was equivalent between wild-type and homozygous embryos after RA treatment. RA treatment also did not distinguish between wild-type and RXR alpha -/- embryos in the spatial expression of sonic hedgehog (Shh) and hoxd-12, two other genes implicated in limb development. However, the quantitative level of hoxd-12 expression was elevated in RXR alpha -/- embryos. These observations indicate that transcriptional processes which are inappropriately regulated in the mouse limb by exogenous RA require RXR alpha for their execution, and that specific teratogenic processes, as well as specific normal developmental processes under vitamin A control, occur through individual members of the RXR and RAR families.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


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
 Toxicol SciHome page
S. E. Ali-Khan and B. F. Hales
Retinoid Receptor Antagonists Alter the Pattern of Apoptosis in Organogenesis Stage Mouse Limbs
Toxicol. Sci., March 1, 2006; 90(1): 208 - 220.
[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
R. A. Schneider, D. Hu, J. L. R. Rubenstein, M. Maden, and J. A. Helms
Local retinoid signaling coordinates forebrain and facial morphogenesis by maintaining FGF8 and SHH
Development, July 15, 2001; 128(14): 2755 - 2767.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. A. Ross, P. J. McCaffery, U. C. Drager, and L. M. De Luca
Retinoids in Embryonal Development
Physiol Rev, July 1, 2000; 80(3): 1021 - 1054.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
V. Giguère
Orphan Nuclear Receptors: From Gene to Function
Endocr. Rev., October 1, 1999; 20(5): 689 - 725.
[Abstract] [Full Text]

Home page
 J. Lipid Res.Home page
H. H. Steineger, B. M. Arntsen, O. Spydevold, and H. N. Sørensen
Gene transcription of the retinoid X receptor {alpha} (RXR{alpha}) is regulated by fatty acids and hormones in rat hepatic cells
J. Lipid Res., April 1, 1998; 39(4): 744 - 754.
[Abstract] [Full Text]

Home page
 JCBHome page
D. E. Cash, C. B. Bock, K. Schughart, E. Linney, and T. M. Underhill
Retinoic Acid Receptor alpha  Function in Vertebrate Limb Skeletogenesis: a Modulator of Chondrogenesis
J. Cell Biol., January 27, 1997; 136(2): 445 - 457.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
X Feng, Z H Peng, W Di, X Y Li, C Rochette-Egly, P Chambon, J J Voorhees, and J H Xiao
Suprabasal expression of a dominant-negative RXR alpha mutant in transgenic mouse epidermis impairs regulation of gene transcription and basal keratinocyte proliferation by RAR-selective retinoids.
Genes & Dev., January 1, 1997; 11(1): 59 - 71.
[Abstract] [PDF]


© The Company of Biologists Ltd 1995