| Project/Area Number |
08671358
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NISHIMURA Yoshihiko KYOTO UNIVERSITY Faculty of Med. Prof., 医学研究科, 教授 (50081790)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAWAKI Yoshio KYOTO UNIVERSITY Faculty of Med., Assisstant, 医学研究科, 助手 (40263074)
SUZUKI Yoshihisa KYOTO UNIVERSITY Faculty of Med., Assisstant Professor, 医学研究科, 講師 (30243025)
MORI Chisato KYOTO UNIVERSITY Faculty of Med., Associate Professor., 医学研究科, 助教授 (90174375)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | RARa, b, and g / palatogenesis / cleft palate / Western blot / Northern blot / プログラム細胞死 / 鰓弓 / 二次口蓋形成 |
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| Research Abstract |
Retinoic acid (RA) is mandatory for various biological processes and normal embryonic development, but is teratogenic at high concentrations. RA mediates its effects by RA receptors (RARs) , but the expression of RARs in the developing palate is still unclear. In rodents, one of the major malformations induced by RA is cleft palate (CP) . We investigated the normal expression patterns of RARa, b, and g messenger RNAs (mRNAs) and the effects of all-trans and 13-cis RAs on the expression of RAR mRNAs and proteins in fetal mouse secondary palates. In normal palates, we detected RARa (2.8,3.8kb) , RARb (3.3kb) and RARg (3.7kb) mRNAs.The expression of RARa and g mRNA did not show apparent sequential changes, but that of RARb mRNA increased at GD13.5. Treatment of pregnant mice with 100 mg/kg all-trans RA induced CP in 94% of the fetuses, and elevated RARb and g mRNA levels in their palates, but only RARb protein was up-regulated. Treatment with 100mg/kg 13-cis RA induced CP in 19% of the fetuses, elevated RARb and g mRNA levels, but did not elevate RARb and g proteins. These findings indicate that the induction of RARb mRNA in the fetal palate correlates well with the tissue concentration of all-trans RA after RA treatm ent and RARb may be one of the most influential candidate molecules for RA-induced teratogenesis.
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