| Project/Area Number |
09556073
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KATO Shigeaki Institute of Molecular and Cellular Biosciences, The University of Tokyo, Professor, 分子細胞生物学研究所, 教授 (60204468)
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| Co-Investigator(Kenkyū-buntansha) |
SHIKAMA Hisataka Metabolic Deseases Research, Pharmacology Laboratories, Yamanouchi Pharamaceutic, 薬理研究所・薬理第三研究室, 室長
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 1998: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1997: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | Vitamin A / Vitamin D / nuclear receptor / rickets / enzyme / gene expression / knock-out mouse / genetic disease / 転写促進能 / ホルモン評価系 / 共役因子群 / transient expression系 / ステロイドホルモンレセプター / ステロイドホルモン / バキュロウイルス系 / ホルモン関連化合物 / エンハンサー配列 / エストロゲン(ER) / プレゲステロン(PR) / アンドロゲン(AR) / ミネラルコルチコイド(MR) |
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| Research Abstract |
We studied the molecular mechanism of vitamin A and vitamin D actions in terms of function of their nuclear receptors in intact animals. We generated the VDR KO mice, and they developed only after weaning. Furtherrmore, those mice were crossed with RXRgamma Ko mice to establish double Ko mice for VDR and RXRgamma, and the mice exhibited more over phenotypes, indicating a cross-talk between vitamin A and vitamin D.By means of newly established expression cloning system with the expression cDNA libraly from VDR Ko mice, we cloned for the first time the cDNA of mouse 1alpha-hydroxylase, which is the key enzyme in Vitemin D biosynthesis. Moreover, we demonstrated that genetic nutaion in this gene causes Vitamin D resisttant type I rickets in human.
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