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Generation of mice with bone-specific deficiency of noble vitamin K synthesis enzyme UBIAD1 and elucidation of the physiological roles of UBIAD1.

Research Project

Project/Area Number 26860047
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionSuzuka University of Medical Science

Principal Investigator

HIROTA Yoshihisa  鈴鹿医療科学大学, 薬学部, 助手 (70724277)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsビタミンK / UBIAD1 / 骨代謝 / 骨特異的遺伝子欠損マウス / タンパク質機能解析 / タンパク質構造解析 / 骨特異的ノックアウトマウス
Outline of Final Research Achievements

We have generated mice with bone-specific deficiency of noble vitamin K synthesis enzyme UBIAD1, using mice expressing Cre downstream of the osterix promoter that is specifically expressed in osteoblasts. The lengths and the weights of the generated mice exhibited significantly lower values as compared to those of wild type mice. Further, on performing a functional analysis of UBIAD1, four highly conserved regions were observed across the UBIAD1 variants. A point mutational analysis of UBIAD1 revealed changes in the amino acids involved in cholesterol synthesis and changes in the subcellular localization of UBIAD1. The obtained data has improved clarity on the structure-function relationship of UBIAD1 and the role of the UBIAD1 in bones.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (21 results)

All 2016 2015 2014 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 5 results) Presentation (14 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Synthetic Small Molecules Derived from Natural Vitamin K Homologues that Induce Selective Neuronal Differentiation of Neuronal Progenitor Cells2015

    • Author(s)
      Yoshitomo Suhara,Yoshihisa Hirota, Norika Hanada, Shun Nishina, Sachiko Eguchi, Rie Sakane, Kimie Nakagawa, Akimori Wada, Kazuhiko Takahashi, Hiroaki Tokiwa, and Toshio Okano
    • Journal Title

      J.Med.Chem.

      Volume: 58 (17) Issue: 17 Pages: 7088-7092

    • DOI

      10.1021/acs.jmedchem.5b00999

    • NAID

      130007399590

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Physiological role of vitamin K2 converting enzyme UBIAD1.2015

    • Author(s)
      Hirota Y
    • Journal Title

      Research reports of Suzuka University of Medical Science

      Volume: 22 Pages: 1-17

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ユビキノン生合成に関与する酵素UbiAスーパーファミリーの結晶構造解析2015

    • Author(s)
      廣田佳久, 野田誠司, 西田恵里, 北村幸大, 原田均, 須原義智, 岡野登志夫
    • Journal Title

      ビタミン誌

      Volume: 89 Pages: 579-582

    • NAID

      110010015598

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] YY1 positively regulates human UBIAD1 expression2015

    • Author(s)
      Funahashi N, Hirota Y, Nakagawa K, Sawada N, Watanabe M, Suhara Y, Okano T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: in press Issue: 2 Pages: 238-244

    • DOI

      10.1016/j.bbrc.2015.03.018

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD12015

    • Author(s)
      Hirota Y, Nakagawa K, Sawada N, Okuda N, Suhara Y, Uchino Y, Kimoto T, Funahashi N, Kamao M, Tsugawa N, Okano T.
    • Journal Title

      PLOS ONE.

      Volume: 10 Issue: 4 Pages: e0125737-e0125737

    • DOI

      10.1371/journal.pone.0125737

    • NAID

      130007413127

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice.2014

    • Author(s)
      Nakagawa K, Sawada N, Hirota Y, Uchino Y, Suhara Y, Hasegawa T, Amizuka N, Okamoto T, Tsugawa N, Kamao M, Funahashi N, Okano T
    • Journal Title

      PLoS ONE.

      Volume: 15;9(8) Issue: 8 Pages: e104078-e104078

    • DOI

      10.1371/journal.pone.0104078

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ビタミンK変換酵素UBIAD1タンパク質の機能解析2016

    • Author(s)
      廣田佳久,中川公恵,須原義智,岡野登志夫
    • Organizer
      第136回日本薬学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] PKCシグナル伝達経路の活性化を介してPARP-1はビタミンK2変換酵素UBIAD1遺伝子を正に制御する2015

    • Author(s)
      廣田佳久,中川公恵,渡辺雅人,須原義智,岡野登志夫
    • Organizer
      第88回 日本分子生物学会・日本生化学会合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] PKCシグナル伝達経路の活性化を介してPARP-1はビタミンK2合成酵素UBIAD1遺伝子を正に制御する2015

    • Author(s)
      廣田佳久,中川公恵,渡辺雅人,須原義智,岡野登志夫
    • Organizer
      フォーラム2015:衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸学院大学 ポートアイランドキャンパス
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] ビタミンK2変換酵素UBIAD1の発現制御機構の解析2015

    • Author(s)
      廣田佳久、中川公恵、柴原貴哉、坂晋、里見佳子、原田均、大西志保、川西正祐、岡野登志夫
    • Organizer
      第61回 日本薬学会東海支部大会
    • Place of Presentation
      名古屋市立大学薬学部
    • Year and Date
      2015-07-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] PKC活性化剤PMAはビタミンK変換酵素UBIAD1遺伝子を正に制御する2015

    • Author(s)
      廣田佳久,中川公恵,渡辺雅人,須原義智,岡野登志夫
    • Organizer
      第67回 日本ビタミン学会
    • Place of Presentation
      奈良県新公会堂
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] ビタミンK2 合成酵素Ubiad1 遺伝子欠損マウスは胎生致死となる2015

    • Author(s)
      中川公恵、澤田夏美、廣田佳久、内野由理、須原義智、岡野登志夫
    • Organizer
      日本薬学会年会
    • Place of Presentation
      神戸サンボーホール
    • Year and Date
      2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] PARP-1はビタミンK変換酵素UBIAD1遺伝子の転写を促進する2015

    • Author(s)
      廣田佳久、中川公恵、渡辺雅人、須原義智、岡野登志夫
    • Organizer
      日本薬学会年会
    • Place of Presentation
      神戸サンボーホール
    • Year and Date
      2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] ニューロンへの分化を誘導する新規ビタミンK 誘導体の合成と簡便な活性評価法2015

    • Author(s)
      坂根里枝、 石澤通康、木村キミト、大西創、廣田佳久、中川公恵、岡野登志夫、槇島誠、須原義智
    • Organizer
      日本薬学会年会
    • Place of Presentation
      デザイン・クリエーティブセンター神戸
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Menadione Is a Catabolic Product of Oral Phylloquinone in the Intestine and a Circulating Precursor of Tissue Menaquinone-4 in Rats2014

    • Author(s)
      Yoshihisa Hirota
    • Organizer
      ネスレ栄養科学会議
    • Place of Presentation
      東京大学 伊藤謝恩ホール
    • Year and Date
      2014-11-15
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ヒトおよびラットにおけるビタミンK側鎖切断酵素の探索2014

    • Author(s)
      廣田佳久、津川尚子、中川公恵、鎌尾まや、須原義智、岡野登志夫
    • Organizer
      日本生化学
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2014-10-16
    • Related Report
      2014 Research-status Report
  • [Presentation] ビタミンK変換酵素の発現制御機構に関する研究2014

    • Author(s)
      廣田佳久、中川公恵、渡辺雅人、舟橋伸昭、岡野登志夫
    • Organizer
      日本薬学会環境・衛生部会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2014-09-19
    • Related Report
      2014 Research-status Report
  • [Presentation] ビタミンK生体内代謝機構の解明2014

    • Author(s)
      廣田佳久、津川尚子、中川公恵、鎌尾まや、内野由理、須原義智、岡野登志夫
    • Organizer
      日本薬学会東海支部
    • Place of Presentation
      鈴鹿医療科学大学 白子キャンパス
    • Year and Date
      2014-07-05
    • Related Report
      2014 Research-status Report
  • [Presentation] ビタミンK側鎖切断組織の同定と側鎖切断体の探索2014

    • Author(s)
      津川尚子、廣田佳久、中川公恵、鎌尾まや、内野由理、須原義智、沖津貴志、和田昭盛、岡野登志夫
    • Organizer
      ビタミン学会
    • Place of Presentation
      姫路商工会議所
    • Year and Date
      2014-06-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 円二色性分散計を用いた核内受容体SXRの脂溶性ビタミン認識特性の解析2014

    • Author(s)
      木本貴士、廣田佳久、舟橋伸昭、中川公恵、和田昭盛、岡野登志夫
    • Organizer
      ビタミン学会
    • Place of Presentation
      姫路商工会議所
    • Year and Date
      2014-06-13
    • Related Report
      2014 Research-status Report
  • [Remarks] 鈴鹿医療科学大学 シーズ集

    • URL

      http://suzuka-u.jpn.org/contents/detail.php?mid=20140624-134358&t=c&url=%E5%8C%BB%E5%AD%A6%E3%83%BB%E8%96%AC%E5%AD%A6

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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