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, Taichi Noda Division of Reproductive Biology, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Priority Organization for Innovation and Excellence, Kumamoto University , Kumamoto, Kumamoto , Japan Department of Experimental Genome Research, Research Institute for Microbial Diseases , Osaka University, Suita, Osaka , Japan Correspondence: Division of Reproductive Biology, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, Kumamoto 860-0811, Japan. E-mail: noda-t@kumamoto-u.ac.jp; Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: ikawa@biken.osaka-u.ac.jp Search for other works by this author on: Oxford Academic Hina Shinohara Division of Reproductive Biology, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Division of Developmental Genetics, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Search for other works by this author on: Oxford Academic Sumire Kobayashi Department of Experimental Genome Research, Research Institute for Microbial Diseases , Osaka University, Suita, Osaka , Japan Search for other works by this author on: Oxford Academic Ayumu Taira Division of Reproductive Biology, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Division of Developmental Genetics, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Search for other works by this author on: Oxford Academic Seiya Oura Department of Experimental Genome Research, Research Institute for Microbial Diseases , Osaka University, Suita, Osaka , Japan Search for other works by this author on: Oxford Academic Duri Tahara Division of Reproductive Biology, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Search for other works by this author on: Oxford Academic Midori Tokuyasu Division of Developmental Genetics, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Search for other works by this author on: Oxford Academic Kimi Araki Division of Developmental Genetics, Institute of Resource Development and Analysis , Kumamoto University, Kumamoto, Kumamoto , Japan Center for Metabolic Regulation of Healthy Aging, Kumamoto University , Kumamoto, Kumamoto , Japan Search for other works by this author on: Oxford Academic Masahito Ikawa Department of Experimental Genome Research, Research Institute for Microbial Diseases , Osaka University, Suita, Osaka , Japan Correspondence: Division of Reproductive Biology, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, Kumamoto 860-0811, Japan. E-mail: noda-t@kumamoto-u.ac.jp; Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: ikawa@biken.osaka-u.ac.jp Search for other works by this author on: Oxford Academic
Biology of Reproduction, Volume 110, Issue 4, April 2024, Pages 750–760, https://doi.org/10.1093/biolre/ioae008
Published:
13 January 2024
Article history
Received:
05 July 2023
Revision received:
30 November 2023
Accepted:
09 January 2024
Published:
13 January 2024
Corrected and typeset:
03 February 2024
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Taichi Noda, Hina Shinohara, Sumire Kobayashi, Ayumu Taira, Seiya Oura, Duri Tahara, Midori Tokuyasu, Kimi Araki, Masahito Ikawa, Multiple genes in the Pate5–13 genomic region contribute to ADAM3 processing, Biology of Reproduction, Volume 110, Issue 4, April 2024, Pages 750–760, https://doi.org/10.1093/biolre/ioae008
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Abstract
Sperm proteins undergo post-translational modifications during sperm transit through the epididymis to acquire fertilizing ability. We previously reported that the genomic region coding Pate family genes is key to the proteolytic processing of the sperm membrane protein ADAM3 and male fertility. This region contains nine Pate family genes (Pate5–13), and two protein-coding genes (Gm27235 and Gm5916), with a domain structure similar to Pate family genes. Therefore, in this study, we aimed to identify key factors by narrowing the genomic region. We generated three knockout (KO) mouse lines using CRISPR/Cas9: single KO mice of Pate10 expressed in the caput epididymis; deletion KO mice of six caput epididymis-enriched genes (Pate5–7, 13, Gm27235, and Gm5916) (Pate7-Gm5916 KO); and deletion KO mice of four genes expressed in the placenta and epididymis (Pate8, 9, 11, and 12) (Pate8–12 KO). We observed that the fertility of only Pate7-Gm5916 KO males was reduced, whereas the rest remained unaffected. Furthermore, when the caput epididymis-enriched genes, Pate8 and Pate10 remained in Pate7-Gm5916 KO mice were independently deleted, both KO males displayed more severe subfertility due to a decrease in mature ADAM3 and a defect in sperm migration to the oviduct. Thus, our data showed that multiple caput epididymis-enriched genes within the region coding Pate5–13 cooperatively function to ensure male fertility in mice.
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© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
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