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Validation of a mechanism for the pathogenesis of multiple cystic kidney disease based on DNA mutations induced by dietary stimulation.

Research Project

Project/Area Number 18K11141
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionFujita Health University

Principal Investigator

Kugita Masanori  藤田医科大学, 病態モデル先端医学研究センター, 講師 (50440681)

Co-Investigator(Kenkyū-buntansha) 熊本 海生航  藤田医科大学, 病態モデル先端医学研究センター, 講師 (10469322)
吉村 文  藤田医科大学, 病態モデル先端医学研究センター, 講師 (90466483)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordspolycystic kidney / animal model / 多発性嚢胞腎症 / モデル動物
Outline of Final Research Achievements

Polycystic kidney disease (PKD) is caused by mutations in the PKD1 gene. Approximately 11% of PKD1 mutations are nonsense mutations, which stop translation, and the majority of the rest are amino acid substitution mutations. Nonsense mutations cause more severe PKD. However, it was not known which sites of amino acid substitution mutations influence the pathogenesis of PKD. Therefore, we generated several knock-in mice carrying a single amino acid mutation in the Pkd1 gene and analyzed them to determine the effect of the mutation on the pathogenesis of PKD.

Academic Significance and Societal Importance of the Research Achievements

腎臓に多数の嚢胞ができる多発性嚢胞腎症(PKD)は、PKD1及びPKD2遺伝子に変異が入ることにより発症する。本研究では、PKD1及びPKD2遺伝子産物が作る複合体の構造とヒトPKD患者のデータベースを参照することに各種Pkd1ノックインマウスを作成して、1アミノ酸を変えるだけでPKDの病態が異なることを示した。これらPkd1ノックインマウスを用いてPkd1遺伝子の機能解析を進めていけば、PKDの発症機序や新規治療薬の開発につながると考える。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2022 2021 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] High Levels of Dietary Lard or Sucrose May Aggravate Lysosomal Renal Injury in Non-Obese, Streptozotocin-Injected CD-1 Mice Provided Isocaloric Diets2021

    • Author(s)
      YOSHIMURA Aya、YAMAGUCHI Tamio、KUGITA Masanori、KUMAMOTO Kanako、SHIOGAMA Kazuya、OGITSU Naomichi、YONEDA Misao、MIURA Toshihiro、NAGAMURA Yoichi、NAGAO Shizuko
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 67 Issue: 4 Pages: 243-248

    • DOI

      10.3177/jnsv.67.243

    • NAID

      130008080674

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2021-08-31
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased salt intake does not worsen the progression of renal cystic disease in high water-loaded PCK rats.2019

    • Author(s)
      Shizuko Nagao, Masanori Kugita, Kanako Kumamoto, Aya Yoshimura, Kazuhiro Nishii, Tamio Yamaguchi.
    • Journal Title

      PLoS One.

      Volume: 14(3) Issue: 3 Pages: e0207461-e0207461

    • DOI

      10.1371/journal.pone.0207461

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 食塩感受性高血圧の遺伝的背景を伴う多発性嚢胞腎症ラットの病態解析2022

    • Author(s)
      吉村文, 松山依里子, 坂田美和, 白水貴大, 釘田雅則, 熊本海生航, 平林真澄, 長尾静子
    • Organizer
      第69回日本実験動物学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 3.Altered cellular signaling pathways identified by proteomics and phosphor-proteomics in a rat model of diabetic kidney disease.2021

    • Author(s)
      Aya Yoshimura, Masanori Kugita, Hisateru Yamaguchi, Kazuki Nakajima, Kanako Kumamoto, Tamio Yamaguchi, Kazuo Takahashi, Yukio Yuzawa, Shizuko Nagao
    • Organizer
      Kidney Week 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparison of the effect of calorie matched high saturated-fat and high unsaturated-fat diets on lysosomal renal injury in non-obese, streptozotocin-injected CD-1 mice2020

    • Author(s)
      Tamio Yamaguchi, Aya Yoshimura, Masanori Kugita, Kanako Kumamoto, Kazuya Shiogama, Kyongtae T. Bae, Shizuko Nagao
    • Organizer
      Kidney week
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 食塩感受性高血圧の遺伝的背景を持つ新規ARPKDモデル動物2020

    • Author(s)
      吉村 文、釘田 雅則、熊本 海生航、坂田 美和、長尾 静子
    • Organizer
      第63回日本腎臓学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 同一摂取カロリーでラードとスクロースの比率を高めた場合の非肥満糖尿病マウスの血糖動態と腎傷害発現2020

    • Author(s)
      吉村 文, 山口 太美雄, 釘田 雅則, 熊本 海生航, 塩竈 和也, 荻津 直通, 三浦 俊宏, 米田 操, 長村 洋一, 長尾 静子
    • Organizer
      第63回日本腎臓学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] ネフロン癆モデル動物pcyマウスの多発性嚢胞腎における代謝産物の網羅的解析2019

    • Author(s)
      釘田 雅則、熊本 海生航、吉村 文、中嶋 和紀、高橋 和男、湯澤 由紀夫、長尾 静子
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 2種類の繊毛病モデル動物を用いた多発性嚢胞腎における代謝産物の網羅的解析2019

    • Author(s)
      釘田 雅則、熊本 海生航、吉村 文、中嶋 和紀、高橋 和男、湯澤 由紀夫、長尾 静子
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 多発性嚢胞腎症モデル動物PCKラットにおける嚢胞形成関連代謝産物の探索2019

    • Author(s)
      釘田 雅則、熊本 海生航、吉村 文、長尾 静子
    • Organizer
      第90回東海実験動物研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Glucose metabolic profiles in renal tissue of an orthologous PCK rat model of human PKD using metabolic and proteomic analyses.2018

    • Author(s)
      Shizuko Nagao, Masanori Kugita, Kanako Kumamoto, Aya Yoshimura, Tamio Yamaguchi, Kazuki Nakajima, Kazuo Takahashi, Yukio Yuzawa
    • Organizer
      Kidney week 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mitochondrial Morphological Abnormality in Cyst Epithelial Cells of Autosomal Dominant Polycystic Kidney Disease Patients.2018

    • Author(s)
      Yu Ishimoto, Akira Shimizu, Masanori Kugita, Shizuko Nagao, Kenjiro Honda, Reiko Inagi, Masanomi Nangaku, Saori Nishio, Haruna Kawano, Shigeo Horie, Tomoko Kasahara, Kenji Osafune, Junichi Hoshino, Yoshifumi Ubara
    • Organizer
      Kidney week 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多発性嚢胞腎症モデル動物PCKラットの腎臓における代謝産物解析~中心炭素代謝経路について~2018

    • Author(s)
      釘田雅則、熊本海生航、吉村 文、中嶋和紀、高橋和男、湯澤由紀夫、長尾静子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 多発性嚢胞腎症モデルPCKラットの腎臓におけるメタボローム解析―グルコース代謝経路についてー2018

    • Author(s)
      釘田雅則、熊本海生航、吉村 文、山口太美雄、長尾静子
    • Organizer
      第65回日本実験動物学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 嚢胞性腎疾患モデルラットの腎臓における嚢胞形成と一次繊毛長の関係2018

    • Author(s)
      熊本海生航、吉村 文、釘田雅則、長尾静子
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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