PMID- 10100049
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20131121
IS  - 0270-4145 (Print)
IS  - 0270-4145 (Linking)
VI  - 18
IP  - 4
DP  - 1998 Oct-Dec
TI  - Altered expression of retinoic acid (RA) receptor mRNAs in the fetal mouse 
      secondary palate by all-trans and 13-cis RAs: implications for RA-induced 
      teratogenesis.
PG  - 202-10
AB  - Retinoic acid (RA) is mandatory for various biological processes and normal 
      embryonic development but is teratogenic at high concentrations. In rodents, one 
      of the major malformations induced by RA is cleft palate (CP). RA mediates its 
      effects by RA receptors (RARs), but the expression patterns of RARs in the 
      developing palate are still unclear. We investigated the normal expression of RAR 
      alpha, beta, and gamma messenger RNAs (mRNAs) in the fetal mouse secondary palate 
      and the effects of all-trans and 13-cis RAs on the expression of RAR mRNAs by 
      Northern blot analysis. RAR alpha (2.8, 3.8 kb), RAR beta (3.3 kb), and RAR gamma 
      (3.7 kb) mRNAs were detected in the fetal palate on gestational days (GD) 
      12.5-14.5. The expression of RAR alpha and gamma mRNAs did not show apparent 
      sequential changes, but that of RAR beta mRNA increased at GD 13.5. Treatment of 
      pregnant mice with 100 mg/kg all-trans RA induced CP in 94% of the fetuses and 
      elevated the levels of RAR beta and gamma mRNAs in the fetal palate. The 
      up-regulation of RAR beta mRNA by all-trans RA was more marked than that of RAR 
      gamma mRNA. Treatment with 100 mg/kg 13-cis RA induced CP in only 19% of the 
      fetuses. Although 13-cis RA elevated the RAR beta and gamma mRNA levels in fetal 
      palates, its up-regulation was slower and less marked than that induced by 
      all-trans RA. These findings indicate that the induction of RAR beta mRNA in the 
      fetal palate correlates well with the tissue concentration of all-trans RA after 
      RA treatment, and RAR beta may be one of the most influential candidate molecules 
      for RA-induced teratogenesis.
FAU - Naitoh, H
AU  - Naitoh H
AD  - Department of Anatomy and Developmental Biology, Kyoto University, Faculty of 
      Medicine, Japan.
FAU - Mori, C
AU  - Mori C
FAU - Nishimura, Y
AU  - Nishimura Y
FAU - Shiota, K
AU  - Shiota K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - J Craniofac Genet Dev Biol
JT  - Journal of craniofacial genetics and developmental biology
JID - 8109845
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Teratogens)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Cleft Palate/*chemically induced/embryology/genetics
MH  - Densitometry
MH  - Female
MH  - Gene Expression
MH  - Gestational Age
MH  - Infectious Disease Transmission, Vertical
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Models, Genetic
MH  - Oligonucleotide Probes
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Teratogens/*toxicity
MH  - Time Factors
MH  - Tretinoin/pharmacology/*toxicity
EDAT- 1999/04/01 00:00
MHDA- 1999/04/01 00:01
CRDT- 1999/04/01 00:00
PHST- 1999/04/01 00:00 [pubmed]
PHST- 1999/04/01 00:01 [medline]
PHST- 1999/04/01 00:00 [entrez]
PST - ppublish
SO  - J Craniofac Genet Dev Biol. 1998 Oct-Dec;18(4):202-10.