{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T22:08:30Z","timestamp":1780697310083,"version":"3.54.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"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\/100000057","name":"National Institute of Health General Medical Sciences","doi-asserted-by":"publisher","award":["GM116903"],"award-info":[{"award-number":["GM116903"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Memphis Research Consortium"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sex determination requires the commitment of bipotential gonads to either a testis or an ovarian fate. Gene deletion of the kinase Map3k4 results in gonadal sex reversal in XY mice, and transgenic re-expression of Map3k4 rescues the sex reversal phenotype. Map3k4 encodes a large, multi-functional protein possessing a kinase domain and several, additional protein\u2013protein interaction domains. Although MAP3K4 plays a critical role in male gonadal sex determination, it is unknown if the kinase activity of MAP3K4 is required. Here, we use mice expressing full-length, kinase-inactive MAP3K4 from the endogenous Map3k4 locus to examine the requirement of MAP3K4 kinase activity in sex determination. Although homozygous kinase-inactivation of MAP3K4 (Map3k4KI\/KI) is lethal, a small fraction survive to adulthood. We show Map3k4KI\/KI adults exhibit a 4:1 female-biased sex ratio. Many adult Map3k4KI\/KI phenotypic females have a Y chromosome. XY Map3k4KI\/KI adults with sex reversal display female mating behavior, but do not give rise to offspring. Reproductive organs are overtly female, but there is a broad spectrum of ovarian phenotypes, including ovarian absence, primitive ovaries, reduced ovarian size, and ovaries having follicles in all stages of development. Further, XY Map3k4KI\/KI adults are smaller than either male or female Map3k4WT\/WT mice. Examination of the critical stage of gonadal sex determination at E11.5 shows that loss of MAP3K4 kinase activity results in the loss of Sry expression in XY Map3k4KI\/KI embryos, indicating embryonic male gonadal sex reversal. Together, these findings demonstrate the essential role for kinase activity of MAP3K4 in male gonadal sex determination.<\/jats:p>","DOI":"10.1093\/biolre\/ioab083","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T03:04:43Z","timestamp":1619665483000},"page":"491-502","source":"Crossref","is-referenced-by-count":8,"title":["MAP3K4 kinase activity dependent control of mouse gonadal sex determination"],"prefix":"10.1093","volume":"105","author":[{"given":"Noha A M","family":"Shendy","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Memphis, Memphis, TN, USA"},{"name":"Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber L","family":"Broadhurst","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Memphis, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Memphis, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Read","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Memphis, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy N","family":"Abell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Memphis, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"2021120922431441700_ref1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/wdev.42","article-title":"The molecular and cellular basis of gonadal sex reversal in mice and 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