Elucidatin of the mechanism of oligodontia casued by Wnt mutation using in vivo assay

• Project/Area Number: 20K10227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: The University of Tokushima
• Principal Investigator: YASUE Akihiro 徳島大学, 大学院医歯薬学研究部(歯学域), 徳島大学専門研究員 (80380046)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 歯の発生 / ゲノム編集 / 歯牙欠損症 / Wnt10a / Wnt

Outline of Research at the Start

WNTファミリーメンバーであるWNT10AとWNT10Bは歯牙欠損症の原因遺伝子として同定されたが、それぞれの遺伝子破壊マウスでは歯数減少を示さなかった。一方、我々の作製したそれらダブルノックアウトマウスでは一部歯の欠損を認めた。本研究では、WNTと歯の発生に関して、ゲノム編集技術を利用しながら、遺伝子機能喪失と歯牙欠損に関する分子的理解を深化させることを目指す。

Outline of Final Research Achievements

Although Wnt10A and Wnt10B have been reported as causative genes of human dentition, knockout (KO) mice do not cause tooth loss. When created, unlike the original deletion mutant, the maxillary incisors and third molars were deleted. The maxillary second molars and mandibular incisors were also dwarfed, and the crown morphology was flat and taurodont-like in Wnt10a-/-. This result also suggests functional overlap/complementation between Wnt10a and Wnt10b paralogues.

Academic Significance and Societal Importance of the Research Achievements

Wnt10aとWnt10bそれぞれのシングルノックKOマウスでは歯数減少を示さなかったが、ダブル変異体では歯数の様々なバリエーションが示された。ダブルKOマウスを作製したところ、単独欠失変異体と異なり、上顎切歯・第三臼歯が欠失した。上顎第二臼歯・下顎切歯も矮小化しており、また、歯冠形態はWnt10a-/-同様平坦でタウロドントを呈し、さらに各々の変異体では認められなかった体長の減少も生じた。この結果は、Wnt10aとWnt10bのパラログ間での機能の重複・補完を示唆するものでもある。

Research Products

• [Journal Article] Effects of Wnt10a and Wnt10b Double Mutations on Tooth Development (2023)
  • Author(s): Yoshinaga Kaoru、Yasue Akihiro、Mitsui Silvia Naomi、Minegishi Yoshiyuki、Oyadomari Seiichi、Imoto Issei、Tanaka Eiji
  • Journal Title: Genes Volume: 14 Issue: 2 Pages: 340-340
  • DOI: 10.3390/genes14020340
  • Peer Reviewed
• [Journal Article] Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity (2021)
  • Author(s): Miyake Masato、Zhang Jun、Yasue Akihiro、Hisanaga Satoshi、Tsugawa Kazue、Sakaue Hiroshi、Oyadomari Miho、Kiyonari Hiroshi、Oyadomari Seiichi
  • Journal Title: iScience Volume: 24 Issue: 12 Pages: 103448-103448
  • DOI: 10.1016/j.isci.2021.103448
  • Peer Reviewed / Open Access
• [Presentation] In vivo elucidation of the effect on the number of teeth caused by double mutant of Wnt10a and Wnt10b (2020)
  • Author(s): Kaoru Yoshinata, Akihiro Yasue, Eiji Tanaka
  • Organizer: International Orthodontic Congress
  • Int'l Joint Research