{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:17:47Z","timestamp":1792509467587,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM139784"],"award-info":[{"award-number":["T32GM139784"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS094596"],"award-info":[{"award-number":["R01NS094596"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS115017"],"award-info":[{"award-number":["R01NS115017"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS129784"],"award-info":[{"award-number":["R01NS129784"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Brain somatic variants in <jats:italic>SLC35A2<\/jats:italic> were recently identified as a genetic marker for mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). The role of <jats:italic>SLC35A2<\/jats:italic> in cortical development and the contributions of abnormal neurons and oligodendrocytes to seizure activity in MOGHE remain largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we generated a novel <jats:italic>Slc35a2<\/jats:italic> floxed allele, which we used to develop two <jats:italic>Slc35a2<\/jats:italic> conditional knockout mouse lines targeting (1) the <jats:italic>Emx1<\/jats:italic> dorsal telencephalic lineage (excitatory neurons and glia) and (2) the <jats:italic>Olig2<\/jats:italic> lineage (oligodendrocytes). We examined brain structure, behavior, and seizure activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Knockout of <jats:italic>Slc35a2<\/jats:italic> from the <jats:italic>Emx1<\/jats:italic> lineage, which targets both cortical neurons and oligodendrocytes, resulted in early lethality and caused abnormal cortical development, increased oligodendroglial cell density, early onset seizures, and developmental delays akin to what is observed in patients with MOGHE. By tracing neuronal development with 5\u2010Ethynyl\u20102'\u2010deoxyuridine (EdU) birthdating experiments, we found that <jats:italic>Slc35a2<\/jats:italic> deficiency disrupts corticogenesis by delaying radial migration of neurons from the subventricular zone. To discern the contributions of oligodendrocytes to these phenotypes, we knocked out <jats:italic>Slc35a2<\/jats:italic> from the <jats:italic>Olig2<\/jats:italic> lineage. This recapitulated the increased oligodendroglial cell density and resulted in abnormal electroencephalographic activity, but without a clear seizure phenotype, suggesting <jats:italic>Slc35a2<\/jats:italic> deficiency in neurons is required for epileptogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study presents two novel <jats:italic>Slc35a2<\/jats:italic> conditional knockout mouse models and characterizes the effects on brain development, behavior, and epileptogenesis. Together, these results demonstrate a direct causal role for <jats:italic>SLC35A2<\/jats:italic> in MOGHE\u2010like phenotypes, including a critical role in neuronal migration during brain development, and identify neurons as key contributors to <jats:italic>SLC35A2<\/jats:italic>\u2010related epileptogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18166","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T12:39:47Z","timestamp":1729946387000},"page":"3717-3731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mouse models of <i>Slc35a2<\/i> brain mosaicism reveal mechanisms of mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy"],"prefix":"10.1111","volume":"65","author":[{"given":"Hyojung","family":"Yoon","sequence":"first","affiliation":[{"name":"Institute for Genomic Medicine Nationwide Children's Hospital  Columbus Ohio 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