PMID- 12782789
OWN - NLM
STAT- MEDLINE
DCOM- 20030722
LR  - 20231105
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 100
IP  - 12
DP  - 2003 Jun 10
TI  - Retinoid activation of retinoic acid receptor but not retinoid X receptor is 
      sufficient to rescue lethal defect in retinoic acid synthesis.
PG  - 7135-40
AB  - 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.
FAU - Mic, Felix A
AU  - Mic FA
AD  - OncoDevelopmental Biology Program, Burnham Institute, 10901 North Torrey Pines 
      Road, La Jolla, CA 92037, USA.
FAU - Molotkov, Andrei
AU  - Molotkov A
FAU - Benbrook, Doris M
AU  - Benbrook DM
FAU - Duester, Gregg
AU  - Duester G
LA  - eng
GR  - R01 GM062848/GM/NIGMS NIH HHS/United States
GR  - R01 GM062848-01A2/GM/NIGMS NIH HHS/United States
GR  - CA77711/CA/NCI NIH HHS/United States
GR  - GM62848/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030602
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Ligands)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.2.- (Aldehyde Oxidoreductases)
RN  - EC 1.2.1.36 (RALDH2 protein, mouse)
SB  - IM
MH  - Aldehyde Oxidoreductases/*deficiency/genetics
MH  - Alitretinoin
MH  - Animals
MH  - Embryo, Mammalian/metabolism
MH  - Female
MH  - Ligands
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Pregnancy
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Retinoid X Receptors
MH  - Retinoids/*metabolism
MH  - Signal Transduction
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcriptional Activation
MH  - Tretinoin/*metabolism
PMC - PMC165842
EDAT- 2003/06/05 05:00
MHDA- 2003/07/23 05:00
PMCR- 2003/12/10
CRDT- 2003/06/05 05:00
PHST- 2003/06/05 05:00 [pubmed]
PHST- 2003/07/23 05:00 [medline]
PHST- 2003/06/05 05:00 [entrez]
PHST- 2003/12/10 00:00 [pmc-release]
AID - 1231422100 [pii]
AID - 1007135 [pii]
AID - 10.1073/pnas.1231422100 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7135-40. doi: 
      10.1073/pnas.1231422100. Epub 2003 Jun 2.