1998 Fiscal Year Final Research Report Summary
Molecular mechanism of vitamin A and vitamin D actions
| 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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| Keywords | Vitamin A / Vitamin D / nuclear receptor / rickets / enzyme / gene expression / knock-out mouse / genetic disease |
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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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[Publications] Sekine, K., Ohuchi, H., Fujiwara, M., Yamasaki, M., Yoshizawa, T., Sato, T., Yagishita, N., Matsui, D., Koga, Y., Itoh, N., Kato, S.: "FGF10 is essential for the limb and lung formation." Nature Genetics. 21. 138-141 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Takeyama, K., Masuhiro, Y., Fuse, H., Endoh, H., Murayama, A., Kitanaka, S., Suzawa, M., Yanagisawa, J., Kato, S.: "Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog." Mol.Cell.Biol.(in press). (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Yanagisawa, J., Yanagi, Y., Masuhiro, Y., Suzawa, M., Toriyabe, T., Kashiwagi, K., Watanabe, M., Kawabata, M., Miyazono, K., Kato, S.: "Convergence of TGFbeta and vitamin D signaling pathways on SMAD proteins acting as common transcriptional co-activators." Science. 283. 1317-1321 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Takeda, S., Yoshizawa, T., Nagai, Y., Yamato, H., Fukumoto, S., Sekine, K., Kato, S., Matsumoto, T., Fujita, T.: "Stimulation of osteoclast formation by1,25-dihydroxyvitamin D requirs its binding to vitamin D receptor (VDR) in osteoblastic cells : Studies using VDR knockout mice." Endocrinology. (in press). (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kitanaka, S., Takeyama, K., Murayama, A., Sato, T., Okumura, K., Nagami, M., Hasegawa, Y., Niimi, H., Yanagisawa, J., Tanaka, T., Kato, S.: "Inactivating mutations in the human 25-hydroxyvitamin D_3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficient rickets." N.Engl.J.Med.338. 653-661 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Harada, H., Kuboi, Y., Miki, R., Honda, C., Masushige, S., Nakatsuka, M., Koga, Y., Kato, S.: "Cloning of rabbit TR4 and its bone cell-specific activity to suppress estrogen receptor-mediated transactivation." Endocrinology. 139. 204-212 (1998)
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「研究成果報告書概要(欧文)」より
