| Project/Area Number |
17K15261
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied biochemistry
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| Research Institution | Toyama Prefectural University |
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Principal Investigator |
Yasuda Kaori 富山県立大学, 工学部, 助教 (70707231)
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| Research Collaborator |
Sakaki Toshiyuki
Ikushiro Shinichi
Nishikawa Miyu
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ビタミンD / 代謝 / ゲノム編集 / 遺伝子改変ラット |
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| Outline of Final Research Achievements |
It is known that CYP27B1 dysfunction caused bone disease, because 25-hydroxyvitamin D3 (25D3) in the body could not metabolized to active vitamin D3 (1α, 25-hydroxyvitamin D3). Although administration of an active vitamin D3 recovers the bone disease such as rickets, the better compounds which have fewer side effects are desired. In this study, we clarified that daily administration of 25D3 to CYP27B1 gene-deficient mice and rats restores the rickets-like phenotype. As a result of further studies, it is demonstrated that CYP27A1 in the liver complementarily performs 1α-hydroxylation of 25D3 and produced the normal amount of active vitamin D3 in CYP27B1-KO mice and rats. Our results demonstrated that administration of 25D3 may be a new treatment with few side effects for the treatment of type I rickets.
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| Academic Significance and Societal Importance of the Research Achievements |
I型くる病は活性型ビタミンDの低下により引き起こされる骨疾患であることから、活性型ビタミンD3製剤がその治療薬として使用されているが、より副作用の少ない治療薬が求められている。今回見出した25D3の連日投与では、副作用がみられておらず、25D3がI型くる病の新たな治療薬として有効である可能性を示している。詳細な代謝物解析からその作用メカニズムも明らかにしており、ビタミンDの作用メカニズム解明を行う上で、詳細な代謝解析が重要であることも提案している。
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