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Identification of a novel gene causing cholesterol synthesis deficiency

Research Project

Project/Area Number 17K10044
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

Kikuchi Atsuo  東北大学, 大学病院, 助教 (30447156)

Co-Investigator(Kenkyū-buntansha) 仲川 清隆  東北大学, 農学研究科, 教授 (80361145)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords無毛症 / コレステロール合成経路 / 脂質代謝 / 新規病因遺伝子 / コンディショナルノックアウトマウス / 遺伝学
Outline of Final Research Achievements

Skin lesions, cataracts, and congenital anomalies have been frequently associated with inherited deficiencies in enzymes that synthesize cholesterol, but most of the enzymes have not been reported in humans yet. We had identified a novel candidate gene, LSS, that encodes an enzyme of the same pathway in siblings with congenital hypotrichosis and multiple malformations. In this study, we attempted to genetically and functionally prove the LSS gene deficiency by generating three types of conditional knockout mice that presented skin barrier dysfunction, transient alopecia, and cataract, respectively, all of which reproduced the patient's phenotype. These mice will be useful for understanding the pathogenesis of LSS deficiency in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究ではヒトLSS欠損症の症状を再現するモデルマウスを作成することができた。またヒトやマウスの皮脂・皮膚を使った代謝産物の解析により本疾患における酵素ブロックの証明に成功した。本研究で作成したモデルマウスを用いた今後の研究によって、LSSが欠損した際の病態メカニズムのさらなる解明及び本症への治療法の開発につながることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (1 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice2020

    • Author(s)
      Wada Yoichi、Kikuchi Atsuo、Kaga Akimune、Shimizu Naoki、Ito Junya、Onuma Ryo、Fujishima Fumiyoshi、Totsune Eriko、Sato Ryo、Niihori Tetsuya、Shirota Matsuyuki、Funayama Ryo、Sato Kota、Nakazawa Toru、Nakayama Keiko、Aoki Yoko、Aiba Setsuya、Nakagawa Kiyotaka、Kure Shigeo
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 2 Pages: e1008628-e1008628

    • DOI

      10.1371/journal.pgen.1008628

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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