journal article

Journal Article

Proceedings of the National Academy of Sciences of the United States of America. 2019, 116(37), p. 18498-18506

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

Kita, Kanako

National Academy of Sciences

English

2019-09-10

https://doi.org/10.1073/pnas.1908736116

Fujihara, Y., Noda, T., Kobayashi, K., Oji, A., Kobayashi, S., Matsumura, T., . . . Ikawa, M. (2019). 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, 116(37), 18498-18506. doi:10.1073/pnas.1908736116

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.

© 2019 the Author(s). Published by PNAS. This article is licensed under a Creative Commons Attribution 4.0 International License.

78556

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

National Academy of Sciences

English

2019-09-10

Proceedings of the National Academy of Sciences of the United States of America

116

37

18498

18506

https://doi.org/10.1073/pnas.1908736116

31455729

https://hdl.handle.net/11094/78556