Understanding flagellum formation in mouse spermatozoa

2019 年度 実績報告書

• 研究課題/領域番号: 18K14715
• 研究機関: 大阪大学
• 研究代表者: CASTANEDA JULIO 大阪大学, 微生物病研究所, 特任助教(常勤) (00791659)
• 研究期間 (年度): 2018-04-01 – 2020-03-31
• キーワード: spermatogenesis / flagellum / cilia / sperm motility / fertility / N-DRC

研究実績の概要

My proposal set out the examine cilia and flagella formation by studying 3 components of the Nexin-Dynein Regulatory Complex (N-DRC). The N-DRC is a macromolecular protein complex that helps regulate the beating motion of flagella and cilia as well as their formation. Flagella and cilia are conserved cellular organelles important for cell motility, signaling, embryonic patterning, and organ homeostasis. The N-DRC is composed of 11 subunits (DRC1-11) many of which have been studied in Chlamydomonas, a unicellular green algae. Eight N-DRC components have been studied in mammals leading to various phenotypes such as abnormal organ development (DRC1), short sperm tails (Drc7), immotile sperm (Drc5/Tcte1), or no phenotype at all (Drc6/Fbxl13). The remaining genes yet to be studied include DRC2, 10 (Iqcd), and 11 (Iqca). Using CRISPR/Cas9, I managed to knockout all 3 genes. I found that Drc2 knockout mice are perinatal lethal and exhibit hydrocephalus. Drc11/Iqca mice are fertile with no apparent abnormalities, while Drc10/Iqcd analysis is still ongoing.

研究成果

• [雑誌論文] CRISPR/Cas9-based gene knockout in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction (2020)
  • 著者名/発表者名: Jiang Sun,Yonggang Lu,Kaori Nozawa,Zoulan Xu, Akane Morohoshi,Julio M. Castaneda,Taichi Noda,Haruhiko Miyata, Ferheen Abbasi, Hossam H. Shawki ,Satoru Takahashi,Darius J. Devlin, Zhifeng Yu, Ryan M. Matzuk, Thomas X. Garcia, Martin M. Matzuk, Masahito Ikawa
  • 雑誌名: Biology of Reproduction 巻: 102 ページ: 1-9
  • 査読あり / オープンアクセス
• [雑誌論文] CIB4 Is Essential for the Haploid Phase of Spermatogenesis in Mice (2020)
  • 著者名/発表者名: Zoulan Xu, Haruhiko Miyata, Yuki Kaneda, Julio M Castaneda, Yonggang Lu, Akane Morohoshi, Zhifeng Yu, Martin M Matzuk, Masahito Ikawa
  • 雑誌名: Biology of Reproduction 巻: 102 ページ: 1-9
  • DOI: 10.1093/biolre/ioaa059
  • 査読あり / オープンアクセス
• [雑誌論文] Tesmin, Metallothionein-Like 5, Is Required for Spermatogenesis in Mice (2020)
  • 著者名/発表者名: Asami Oji, Ayako Isotani, Yoshitaka Fujihara, Julio M Castaneda, Seiya Oura, Masahito Ikawa
  • 雑誌名: Biology of Reproduction 巻: 102 ページ: 975-983
  • DOI: 10.1093/biolre/ioaa002
  • 査読あり / オープンアクセス
• [雑誌論文] Mouse T-Complex Protein 11 Is Important for Progressive Motility in Sperm (2019)
  • 著者名/発表者名: Julio M Castaneda, Haruhiko Miyata, Denise R Archambeault, Yuhkoh Satouh, Zhifeng Yu, Masahito Ikawa, Martin M Matzuk
  • 雑誌名: Biology of Reproduction 巻: 102 ページ: 852-862
  • DOI: 10.1093/biolre/ioz226
  • 査読あり / オープンアクセス
• [雑誌論文] CRISPR/Cas9-mediated Genome Editing Reveals 30 Testis-Enriched Genes Dispensable for Male Fertility in Mice (2019)
  • 著者名/発表者名: Y Lu, S Oura, T Matsumura, A Oji, N Sakurai, Y Fujihara, K Shimada, H Miyata, T Tobita, T Noda, J M Castaneda, D Kiyozumi, Q Zhang, T Larasati, S A M Young, M Kodani, C A Huddleston, M J Robertson, C Coarfa, A Isotani, R J Aitken, M Okabe, M M Matzuk, T X Garcia, M Ikawa
  • 雑誌名: Biology of Reproduction 巻: 101 ページ: 501-511
  • DOI: 10.1093/biolre/ioz103
  • 査読あり / オープンアクセス
• [学会発表] Spar1 is a novel transmembrane gene required for acrosome formation in mice (2019)
  • 著者名/発表者名: Julio M Castaneda
  • 学会等名: Society for the Study of Reproduction
  • 国際学会