Study of sperm calcineurin to develop male contraceptive

• Project/Area Number: 16K15687
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Osaka University
• Principal Investigator: IKAWA MASAHITO 大阪大学, 微生物病研究所, 教授 (20304066)
• Co-Investigator(Renkei-kenkyūsha): MIYATA Haruhiko 大阪大学, 微生物病研究所, 助教 (50604732) ; NODA Taichi 大阪大学, 微生物病研究所, 研究員 (50712551)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: カルシニューリン / 避妊薬 / 不妊モデル / ゲノム編集 / 実験動物

Outline of Final Research Achievements

Calcineurin consists of a catalytic subunit and a regulatory subunit. There are 3 ORFs for catalytic subunit (ca, cb, cc) and 2 ORFs for regulatory subunit (r1, r2). We have shown that sperm specific calcineurin (cc/r2) is essential for sperm fertilizing ability so that the specific inhibitor may be used as male contraceptive. In this study, we cloned all 5 human ORFs into mammalian expression vector and succeeded to reconstitute the functional calcineurins in HEK293T cells. Beside, we searched in silico database and listed the 12 candidate proteins as sperm calcineurin specific substrates expressed in testis. Our study paved the way to screen the molecules for male contraceptive.

Research Products

• [Int'l Joint Research] Baylor College of Medicine(米国)
• [Journal Article] Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice. (2016)
  • Author(s): Miyata H, Castaneda JM, Fujihara Y, Yu Z, Archambeault DR, Isotani A, Kiyozumi D, Kriseman ML, Mashiko D, Matsumura T, Matzuk RM, Mori M, Noda T, Oji A, Okabe M, Prunskaite-Hyyrylainen R, Ramirez-Solis R, Satouh Y, Zhang Q, Ikawa M, Matzuk MM.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 113 Issue: 28 Pages: 7704-7710
  • DOI: 10.1073/pnas.1608458113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 受精における精子染色体の局在制御 (2017)
  • Author(s): 宮田治彦
  • Organizer: 第122回日本解剖学会総会・全国学術集会
  • Place of Presentation: 長崎大学坂本キャンパス(長崎県長崎市)
  • Year and Date: 2017-03-30
  • Invited
• [Presentation] 遺伝子改変マウスが切り拓く配偶子研究の未来と臨床応用への展望 (2016)
  • Author(s): 伊川正人
  • Organizer: 第61回日本生殖医学会学術講演会・総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-11-04
  • Invited
• [Book] ゲノム編集技術を使った遺伝子改変マウスの作製 実験医学別冊 マウス表現型解析スタンダード (2016)
  • Author(s): 野田大地，大字亜沙美，伊川正人
  • Total Pages: 9
  • Publisher: 羊土社
• [Remarks] 大阪大学教員基本情報
  • URL: http://www.dma.jim.osaka-u.ac.jp/view?l=ja&u=867