{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:23:01Z","timestamp":1784179381015,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["2020B-1"],"award-info":[{"award-number":["2020B-1"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["20K18208"],"award-info":[{"award-number":["20K18208"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["20K06678"],"award-info":[{"award-number":["20K06678"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["20H04935"],"award-info":[{"award-number":["20H04935"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["20J11355"],"award-info":[{"award-number":["20J11355"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sox9 plays an essential role in mammalian testis formation. It has been reported that gene expression in the testes is regulated by enhancers. Among them, mXYSRa\/Enh13\u2014which is located at far upstream of the transcription start site\u2014plays a critical role, wherein its deletion causes complete male-to-female sex reversal in mice. It has been proposed that the binding sites (BSs) of SOX9 and SRY, the latter of which is the sex determining gene on the Y chromosome, are associated with mXYSRa\/Enh13. They function as an enhancer, whereby the sequences are evolutionarily conserved and in vivo binding of SOX9 and SRY to mXYSRa\/Enh13 has been demonstrated previously. However, their precise in vivo functions have not been examined to date. To this end, this study generated mice with substitutions on the SOX9 and SRY BSs to reveal their in vivo functions. Homozygous mutants of SOX9 and SRY BS were indistinguishable from XY males, whereas double mutants had small testes, suggesting that these functions are redundant and that there is another functional sequence on mXYSRa\/Enh13, since mXYSRa\/Enh13 deletion mice are XY females. In addition, the majority of hemizygous mice with substitutions in SOX9 BS and SRY BS were female and male, respectively, suggesting that SOX9 BS contributes more to SRY BS for mXYSRa\/Enh13 to function. The additive effect of SOX9 and SRY via these BSs was verified using an in vitro assay. In conclusion, SOX9 BS and SRY BS function redundantly in vivo, and at least one more functional sequence should exist in mXYSRa\/Enh13.<\/jats:p>","DOI":"10.1093\/hmg\/ddac184","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T16:58:34Z","timestamp":1659545914000},"page":"55-64","source":"Crossref","is-referenced-by-count":6,"title":["SOX9 and SRY binding sites on mouse mXYSRa\/Enh13 enhancer redundantly regulate <i>Sox9<\/i> expression to varying degrees"],"prefix":"10.1093","volume":"32","author":[{"given":"Yuya","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development , 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 , Japan"},{"name":"Department of NCCHD, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Terao","sequence":"additional","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development , 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-2618","authenticated-orcid":false,"given":"Atsumi","family":"Tsuji-Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development , 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iku","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development , 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 , Japan"},{"name":"Department of NCCHD, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development , 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535 , Japan"},{"name":"Department of NCCHD, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9406-4683","authenticated-orcid":false,"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-ku, Tokyo 157-8535 , Japan"},{"name":"Department of NCCHD, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"2023011312194718500_ref1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.rbmo.2018.03.017","article-title":"Duplication of SOX9 associated with 46,XX ovotesticular disorder of sex development","volume":"37","author":"L\u00f3pez-Hern\u00e1ndez","year":"2018","journal-title":"Reprod. 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A genetically determined mesenchymal disorder combined with sex reversal","volume":"86","author":"Hovm\u00f6ller","year":"1977","journal-title":"Hereditas"},{"key":"2023011312194718500_ref9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF00271160","article-title":"Sex-reversed XY females with campomelic dysplasia are H-Y negative","volume":"57","author":"Bricarelli","year":"1981","journal-title":"Hum. Genet."},{"key":"2023011312194718500_ref10","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/mgg3.165","article-title":"Testicular dysgenesis\/regression without campomelic dysplasia in patients carrying missense mutations and upstream deletion of SOX9","volume":"3","author":"Katoh-Fukui","year":"2015","journal-title":"Mol. Genet. Genomic. 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