{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T02:57:51Z","timestamp":1769309871929,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T00:00:00Z","timestamp":1568419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K06474"],"award-info":[{"award-number":["19K06474"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K18164"],"award-info":[{"award-number":["17K18164"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17930555"],"award-info":[{"award-number":["17930555"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple genes, whose functions or expression are overlapping, compensate for the loss of one gene. A gene cluster in the mouse genome encodes five seminal vesicle proteins (SVS2, SVS3, SVS4, SVS5, and SVS6). These proteins are produced by male rodents and function in formation of the copulatory plug following mating. SVS2 plays an essential role in the successful internal fertilization by protecting the sperm membrane against a uterine immune attack. We hypothesized that the four remaining seminal vesicle proteins (SVPs) of this gene cluster may partially\/completely compensate for the deficiency of SVS2. For confirming our hypothesis, we generated mice lacking the entire SVP-encoding gene cluster and compared their fecundity with Svs2-deficient (Svs2\u2212\/\u2212) mice; that is, mice deficient in Svs2 alone. A single loxP site remained after the deletion of the Svs2 gene. Therefore, we inserted another loxP site by combining the CRISPR\/Cas9 system with single-stranded oligodeoxynucleotides (ssODN). Male mice lacking the entire SVP-encoding gene cluster (Svs2\u20136\u2212\/\u2212 mice) and thereby all five SVP proteins, generated by the deletion of 100kbp genomic DNA, showed low fecundity. However, the fecundity level was comparable with that from Svs2\u2212\/\u2212 male mice. Our results demonstrate that SVS3, SVS4, SVS5, and SVS6 do not function in the protection of sperm against a uterine immune attack in the absence of SVS2. Thus, Svs2 is the critical gene in the SVP gene cluster.<\/jats:p>","DOI":"10.3390\/ijms20184557","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T03:17:57Z","timestamp":1568603877000},"page":"4557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Deletion of a Seminal Gene Cluster Reinforces a Crucial Role of SVS2 in Male Fertility"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3913-4992","authenticated-orcid":false,"given":"Miyuki","family":"Shindo","sequence":"first","affiliation":[{"name":"Division of Laboratory Animal Resources, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-007X","authenticated-orcid":false,"given":"Masafumi","family":"Inui","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Regeneration Systemology, Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Kawasaki, Kanagawa 214-8571, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4880-3406","authenticated-orcid":false,"given":"Woojin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moe","family":"Tamano","sequence":"additional","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai","family":"Tingwei","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory Biology, Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Kawasaki, Kanagawa 214-8571, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Hibino","sequence":"additional","affiliation":[{"name":"Faculty of Education, Saitama University, 255 Shimo-Okubo, Sakura, Saitama, Saitama 338-8570, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4927-868X","authenticated-orcid":false,"given":"Manabu","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Misaki Marine Biological Station, Graduate School of Science, University of Tokyo, 1024 Koajiro, Miura, Kanagawa 238-0225, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9805-2818","authenticated-orcid":false,"given":"Kaoru","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering, Toin University of Yokohama, 1614 Kurogane, Aoba, Yokohama 225-8503, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Urology, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minamikoshigaya, Koshigaya, Saitama 343-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruaki","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Division of Male Infertility, Center for Human Reproduction, Sanno Hospital, International University of Health and Welfare, 8-10-16 Akasaka, Minato, Tokyo 107-0052, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8339-6738","authenticated-orcid":false,"given":"Kenji","family":"Miyado","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuko","family":"Kawano","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory Biology, Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Kawasaki, Kanagawa 214-8571, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/35047605","article-title":"Ancient origin of the Hox gene cluster","volume":"2","author":"Ferrier","year":"2001","journal-title":"Nat. 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