{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T02:40:03Z","timestamp":1750646403172,"version":"3.41.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HD100985"],"award-info":[{"award-number":["1R01HD100985"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Micropenis is a condition with significant physical and psychological implications caused mainly by decreased androgen action in penile development. <jats:italic>Kctd13<\/jats:italic>\u2010knockout (<jats:italic>Kctd13\u2010KO<\/jats:italic>) mice have micropenis, cryptorchidism, and fertility defects because of reduced levels of androgen receptor (AR) and SOX9. We hypothesized that normalizing the levels of AR and SOX9 in the <jats:italic>Kctd13\u2010KO<\/jats:italic> penis could help us to understand the mechanism of action of these signaling pathways on penile development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated transgenic mice lacking <jats:italic>Kctd13<\/jats:italic> and conditionally expressing AR in the urethral mesenchyme after Cre activation with <jats:italic>Twist2<\/jats:italic><jats:sup>cre<\/jats:sup> (<jats:italic>Kctd13\u2010KO<\/jats:italic>; AR\u2010CMV; <jats:italic>Twist2<\/jats:italic><jats:sup>cre<\/jats:sup>; herein called AR+), and Sox9 in the urethral epithelium after Cre activation with <jats:italic>Shh<\/jats:italic><jats:sup>cre<\/jats:sup> (<jats:italic>Kctd13\u2010KO<\/jats:italic>; <jats:italic>Sox9<\/jats:italic>\u2010CAG; <jats:italic>Shh<\/jats:italic><jats:sup>cre<\/jats:sup>; herein called SOX9+). Mice penile morphology, fertility, and the effect of KCTD13 on AR and SOX9 ubiquitination were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p><jats:italic>Kctd13\u2010KO<\/jats:italic> micropenis phenotype was rescued after increasing levels of penile AR or SOX9 as transgenic AR+ and SOX9+ mice have longer penile lengths than <jats:italic>Kctd13\u2010KO<\/jats:italic> mice and are comparable to WT mice. In addition, male\u2010urogenital\u2010mating\u2010protuberance and the baculum were significantly shorter and narrower in <jats:italic>Kctd13\u2010KO<\/jats:italic> mice compared with transgenic AR+ and SOX9+ mice. The position of the urethral meatus was similar and orthotopic in location in <jats:italic>Kctd13\u2010KO<\/jats:italic>, AR+, SOX9+, and WT penises indicating that none of these mice had hypospadias. The subfertility of AR+ and SOX9+ mice was improved. The ectopic expression of KCTD13 in HEK293 cells strongly reduced AR ubiquitination which is abolished when the proteasome pathway is inhibited and this process is mediated by the ubiquitin ligase, STUB1. The effect of KCTD13 on SOX9 ubiquitination is minimal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>KCTD13 regulates AR ubiquitination by modulating STUB1 binding to AR. Penile restoration of AR and SOX9 improved penile development in <jats:italic>Kctd13\u2010KO<\/jats:italic> mice allowing us to discern the contribution from individual signaling pathways and cell types in penile development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.70005","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T07:52:37Z","timestamp":1738223557000},"page":"1201-1212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of Kctd13 in modulating AR and SOX9 expression in different penile cell populations"],"prefix":"10.1111","volume":"13","author":[{"given":"Carolina J.","family":"Jorgez","sequence":"first","affiliation":[{"name":"Scott Department of Urology Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Surgery Nemours Children's Hospital  Orlando Florida USA"},{"name":"University of Central Florida  Orlando Florida 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