Molecular mechanism of vitamin A and vitamin D actions

维生素A和维生素D作用的分子机制

• 批准号: 09556073
• 负责人: KATO Shigeaki
• 金额: $ 8.9万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09556073/
• 关键词: 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)

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.

我们研究了维生素A和维生素D作用的分子机制，在完整的动物核受体的功能。我们产生了VDR KO小鼠，它们仅在断奶后发育。利用新近建立的表达克隆系统，首次克隆了维生素D生物合成的关键酶--小鼠1 α-羟化酶的cDNA。此外，我们还证实了该基因的遗传突变导致了人类维生素D抵抗型佝偻病。

项目成果

Kitanaka,S.,Kato,S.,et al.: "Inactivating mutations in the human 25-hydroxyvitamin D_3 1α-hydroxylase gene in patients with pseudovitamin D-deficient rickets" N. Engl.J.Med.338. 653-661 (1998)

Kitanaka, S.、Kato, S. 等人：“假性维生素 D 缺乏性佝偻病患者中人 25-羟基维生素 D_3 1α-羟化酶基因的失活突变”N. Engl.J.Med.338。 (1998)

Yanagisawa,J.,Kato,S.,et al.: "Convergence of TGFβ and vitamin D signaling pathways on SMAD proteins acting as common transcriptional co-activators" Science. 283. 1317-132〓 (1999)

Yanagisawa, J., Kato, S., et al.：“作为常见转录共激活因子的 SMAD 蛋白上 TGFβ 和维生素 D 信号通路的融合”Science 283. 1317-132〓 (1999)

加 藤 茂 明: "内分泌・代謝疾患(別冊・医学のあゆみ):ステロイド受容体スーパーファミリー" 医歯薬出版株式会社, 566 (1997)

加藤茂晃：《内分泌与代谢疾病（另册/医学史）：类固醇受体超家族》石药出版有限公司，566（1997）

Takeyama,K.,Kato,S.,et al.: "Selective interaction of vitamin Dreceptor with transcriptional coactivators by a vitamin Danalog" Mol.Cell.Biol.(in press). (1999)

Takeyama,K.、Kato,S. 等人：“维生素 Danalog 导致维生素 D 受体与转录共激活剂的选择性相互作用”Mol.Cell.Biol.（出版中）。

Yanagisawa, J., Kato, S., et al.: "Convergence of TGFβ and vitamin D signaling pathways on SMAD proteins acting as common transcriptional co-activators" Science. (in press). (1999)

Yanagisawa, J., Kato, S., et al.：“TGFβ 和维生素 D 信号通路在 SMAD 蛋白上作为常见转录共激活剂的融合”（正在出版）。