In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 12 ( 2003-06-10), p. 7135-7140
Abstract:
Two isomers of retinoic acid (RA) may be necessary as ligands for retinoid signaling: all-trans -RA for RA receptors (RARs) and 9- cis -RA for retinoid X receptors (RXRs). This was explored by using retinaldehyde dehydrogenase ( Raldh)2 -/- mouse embryos lacking mesodermal RA synthesis that display early growth arrest unless rescued by all-trans -RA administration. Because isomerization of all-trans -RA to 9- cis -RA can occur, it is unclear whether both ligands are needed for rescue. We show here that an RAR-specific ligand can rescue Raldh2 -/- embryos as efficiently as all-trans -RA, whereas an RXR-specific ligand has no effect. Further, whereas all-trans -RA was detected in embryos, 9- cis -RA was undetectable unless a supraphysiological dose of all-trans -RA was administered, revealing that 9- cis -RA is of pharmacological but not physiological significance. Because 9- cis -RA is undetectable and unnecessary for Raldh2 -/- rescue, and others have shown that 4-oxo-RA is unnecessary for mouse development, all-trans -RA emerges as the only ligand clearly necessary for retinoid receptor signaling.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1231422100
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2003
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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