{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:53:54Z","timestamp":1790376834812,"version":"4.1.0"},"reference-count":64,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS083897"],"award-info":[{"award-number":["R01NS083897"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["F32NS138224"],"award-info":[{"award-number":["F32NS138224"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R37NS110388"],"award-info":[{"award-number":["R37NS110388"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS120667"],"award-info":[{"award-number":["R01NS120667"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01MH132089"],"award-info":[{"award-number":["R01MH132089"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100002690","name":"Ruth K. Broad Biomedical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002690","id-type":"DOI","asserted-by":"crossref"}]},{"name":"DDX3X Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Heterozygous mutations in the X-linked RNA helicase DDX3X cause DDX3X syndrome, a rare neurodevelopmental disorder associated with cortical malformations and autism spectrum disorder. Among \u223c200 known DDX3X variants, half are missense, while the remainder are predicted loss-of-function (LoF) variants. LoF mouse models reveal that Ddx3x controls progenitors' ability to generate excitatory neurons. Yet, how missense mutations impact corticogenesis in vivo is unknown. Here, we generated a conditional mouse model of DDX3XT532M, a clinically severe and recurrent DDX3X syndrome variant found in affected females. Using Emx1-Cre-mediated expression of Ddx3xT532M in cortical progenitors, we showed that Ddx3xT532M alters corticogenesis. Ddx3xT532M conditional hemizygous males have severe microcephaly and apoptosis. In contrast, Ddx3xT532M conditional heterozygous (cHet) females exhibit mild reductions in cortical size and neurogenesis. Using polysome fractionation of Ddx3xT532M and Ddx3xLoF cHet female cortices, we discovered that Ddx3xT532M affects translation, with Ddx3xT532M cHet females showing qualitative differences from Ddx3xLoF cHet females. Collectively, these findings suggest that although Ddx3xT532M and Ddx3xLoF have similar impacts on corticogenesis in cHet females, they have distinct molecular targets. Our study establishes a new in vivo model for understanding the etiology of DDX3X syndrome.<\/jats:p>","DOI":"10.1242\/dmm.052498","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T09:03:17Z","timestamp":1764320597000},"source":"Crossref","is-referenced-by-count":1,"title":["Impaired cortical development and translational control in a missense mouse model of\n                    <i>DDX3X<\/i>\n                    syndrome"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-4201","authenticated-orcid":false,"given":"Abigail J.","family":"Poff","sequence":"first","affiliation":[{"name":"Duke University Medical Center 1 Department of Molecular Genetics and Microbiology , , Durham, NC 27710 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9920-0560","authenticated-orcid":false,"given":"Nicole D.","family":"Moss","sequence":"additional","affiliation":[{"name":"Duke University Medical Center 1 Department of Molecular Genetics and Microbiology , , Durham, NC 27710 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-844X","authenticated-orcid":false,"given":"Debra L.","family":"Silver","sequence":"additional","affiliation":[{"name":"Duke University Medical Center 1 Department of Molecular Genetics and Microbiology , , Durham, NC 27710 ,","place":["USA"]},{"name":"Duke University Medical Center 2 Department of Neurobiology , , Durham, NC 27710 ,","place":["USA"]},{"name":"Duke University Medical Center 3 Department of Cell Biology , , Durham, NC 27710 ,","place":["USA"]},{"name":"Duke Institute for Brain Sciences and Duke Regeneration Center, Duke University Medical Center 4 , Durham, NC 27710 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"2025112804030908200_DMM052498C1","doi-asserted-by":"publisher","first-page":"114666","DOI":"10.1016\/j.celrep.2024.114666","article-title":"The RNA-binding protein EIF4A3 promotes axon development by direct control of the cytoskeleton","volume":"43","author":"Alsina","year":"2024","journal-title":"Cell Rep."},{"key":"2025112804030908200_DMM052498C2","doi-asserted-by":"publisher","first-page":"3889","DOI":"10.1073\/pnas.0635171100","article-title":"Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae","volume":"100","author":"Arava","year":"2003","journal-title":"Proc. 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