Skip Navigation


ToxSci Advance Access originally published online on December 1, 2005
Toxicological Sciences 2006 90(1):208-220; doi:10.1093/toxsci/kfj060
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
90/1/208    most recent
kfj060v1
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 ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (4)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ali-Khan, S. E.
Right arrow Articles by Hales, B. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ali-Khan, S. E.
Right arrow Articles by Hales, B. F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Retinoid Receptor Antagonists Alter the Pattern of Apoptosis in Organogenesis Stage Mouse Limbs

Sarah E. Ali-Khan and Barbara F. Hales1

Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada H3G 1Y6

Received September 2, 2005; accepted November 21, 2005

Exposure of murine limbs in vitro to vitamin A (retinol) induces limb reduction defects and apoptosis. To assess the relative roles of the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), embryonic-day-12 murine limbs were cultured with selective RAR or RXR antagonists in the presence or absence of teratogenic concentrations of retinol. Both antagonists alone impaired limb development; in the presence of teratogenic concentrations of retinol, both attenuated limb malformations. Abnormal limb morphology, whether caused by excessive or attenuated retinoid signaling by retinol or either antagonist, respectively, was correlated with increased apoptosis after 24 h of drug exposure. We conclude that, in the developing limb, antagonists selective for either member of the RAR/RXR heterodimer attenuate retinoid signaling and block the teratogenic signaling of excess retinol. Improvements in limb morphology in the presence of either the RAR or the RXR antagonist coincided with restoration of the extent and localization of limb bud apoptosis to control patterns.

Key Words: retinoic acid; limb development; limb malformations; teratogen.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
J. M. Rogers
Casting a Broad Network: Fishing for Mechanisms of Retinoid Teratogenicity
Toxicol. Sci., November 1, 2006; 94(1): 1 - 2.
[Full Text] [PDF]

Home page
 Toxicol SciHome page
S. E. Ali-Khan and B. F. Hales
Novel Retinoid Targets in the Mouse Limb during Organogenesis
Toxicol. Sci., November 1, 2006; 94(1): 139 - 152.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.