{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:23:00Z","timestamp":1784179380990,"version":"3.55.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010434","name":"\u201cla Caixa\u201d Foundation","doi-asserted-by":"publisher","award":["LCF\/PR\/HR17\/52150009"],"award-info":[{"award-number":["LCF\/PR\/HR17\/52150009"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["20152210"],"award-info":[{"award-number":["20152210"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2020-119315GB-I00"],"award-info":[{"award-number":["PID2020-119315GB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2020-119322GB-I00"],"award-info":[{"award-number":["PID2020-119322GB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Assessing the role of the WT1 transcription factor (<jats:italic>WT1)<\/jats:italic>during early gonad differentiation and its impact on adult sex development has been difficult due to the complete gonadal agenesis and embryonic lethality exhibited by<jats:italic>Wt1KO<\/jats:italic>mouse models. Here, we generated<jats:italic>Wt1<\/jats:italic><jats:sup><jats:italic>LoxP\/GFP<\/jats:italic><\/jats:sup><jats:italic>;Wt1<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup>mice, the first<jats:italic>Wt1KO<\/jats:italic>mouse model that reaches adulthood with a dramatically reduced<jats:italic>Wt1<\/jats:italic>expression during early gonadogenesis.<jats:italic>Wt1<\/jats:italic><jats:sup><jats:italic>LoxP\/GFP<\/jats:italic><\/jats:sup><jats:italic>;Wt1<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup>mice lacked mature gonads and displayed genital tracts containing both male and female genital structures and ambiguous genitalia. We found that WT1 is necessary for the activation of both male and female sex-determining pathways, as embryonic mutant gonads failed to upregulate the expression of the genes specific for each genetic programme. The gonads of<jats:italic>Wt1<\/jats:italic><jats:sup><jats:italic>LoxP\/GFP<\/jats:italic><\/jats:sup><jats:italic>;Wt1<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup>mice showed a lack of production of Sertoli and pre-granulosa cells and a reduced number of germ cells. NR5A1 and the steroidogenic genes expression was modulated differently in XY and XX<jats:italic>Wt1<\/jats:italic><jats:sup><jats:italic>LoxP\/GFP<\/jats:italic><\/jats:sup><jats:italic>;Wt1<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup>gonads, explaining the mutant phenotypes. Further studies of the XX<jats:italic>Wt1<\/jats:italic><jats:sup><jats:italic>LoxP\/GFP<\/jats:italic><\/jats:sup><jats:italic>;Wt1<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup>gonads revealed that deletion of WT1 at an early stage impaired the differentiation of several cell types including somatic cells and the ovarian epithelium. Through the characterisation of this<jats:italic>Wt1KO<\/jats:italic>mouse model, we show that the deletion of<jats:italic>Wt1<\/jats:italic>during early gonadogenesis produces dramatic defects in adult sex development.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010240","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T18:01:06Z","timestamp":1655316066000},"page":"e1010240","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deletion of Wt1 during early gonadogenesis leads to differences of sex development in male and female adult mice"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-3177","authenticated-orcid":true,"given":"Alejo","family":"Torres-Cano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8495-0470","authenticated-orcid":true,"given":"Rosa","family":"Portella-Fortuny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3654-2683","authenticated-orcid":true,"given":"Claudia","family":"M\u00fcller-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5264-5615","authenticated-orcid":true,"given":"Sonia","family":"Porras-Marfil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9017-4981","authenticated-orcid":true,"given":"Marina","family":"Ramiro-Pareta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8561-8365","authenticated-orcid":true,"given":"You-Ying","family":"Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0701-200X","authenticated-orcid":true,"given":"Manuel","family":"Reina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1678-7162","authenticated-orcid":true,"given":"Francesc X.","family":"Soriano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1814-1974","authenticated-orcid":true,"given":"Ofelia M.","family":"Mart\u00ednez-Estrada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"issue":"2","key":"pgen.1010240.ref001","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1542\/peds.2006-0738","article-title":"Consensus statement on management of intersex disorders. 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