論文

査読有り 本文へのリンクあり
2019年9月10日

Identification of multiple male reproductive tractspecific proteins that regulate sperm migration through the oviduct in mice

Proceedings of the National Academy of Sciences of the United States of America
  • Yoshitaka Fujihara
  • Taichi Noda
  • Kiyonori Kobayashi
  • Asami Oji
  • Sumire Kobayashi
  • Takafumi Matsumura
  • Tamara Larasati
  • Seiya Oura
  • Kanako Kojima-Kita
  • Zhifeng Yu
  • Martin M. Matzuk
  • Masahito Ikawa
  • 全て表示

116
37
開始ページ
18498
終了ページ
18506
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1908736116

© 2019 National Academy of Sciences. All rights reserved. CRISPR/Cas9-mediated genome editing technology enables researchers to efficiently generate and analyze genetically modified animals. We have taken advantage of this game-changing technology to uncover essential factors for fertility. In this study, we generated knockouts (KOs) of multiple male reproductive organspecific genes and performed phenotypic screening of these null mutant mice to attempt to identify proteins essential for male fertility. We focused on making large deletions (dels) within 2 gene clusters encoding cystatin (CST) and prostate and testis expressed (PATE) proteins and individual gene mutations in 2 other gene families encoding glycerophosphodiester phosphodiesterase domain (GDPD) containing and lymphocyte antigen 6 (Ly6)/Plaur domain (LYPD) containing proteins. These gene families were chosen because many of the genes demonstrate male reproductive tract-specific expression. Although Gdpd1 and Gdpd4 mutant mice were fertile, disruptions of Cst and Pate gene clusters and Lypd4 resulted in male sterility or severe fertility defects secondary to impaired sperm migration through the oviduct. While absence of the epididymal protein families CST and PATE affect the localization of the sperm membrane protein A disintegrin and metallopeptidase domain 3 (ADAM3), the sperm acrosomal membrane protein LYPD4 regulates sperm fertilizing ability via an ADAM3-independent pathway. Thus, use of CRISPR/Cas9 technologies has allowed us to quickly rule in and rule out proteins required for male fertility and expand our list of male-specific proteins that function in sperm migration through the oviduct.

リンク情報
DOI
https://doi.org/10.1073/pnas.1908736116
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31455729
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072011217&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85072011217&origin=inward
ID情報
  • DOI : 10.1073/pnas.1908736116
  • ISSN : 0027-8424
  • eISSN : 1091-6490
  • PubMed ID : 31455729
  • SCOPUS ID : 85072011217

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