{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:44:31Z","timestamp":1790246671026,"version":"4.1.0"},"reference-count":91,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001951","name":"Angelman Syndrome Foundation","doi-asserted-by":"crossref","award":["ASF: 10-2018"],"award-info":[{"award-number":["ASF: 10-2018"]}],"id":[{"id":"10.13039\/100001951","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003246","name":"Netherlands Organisation for Scientific Research","doi-asserted-by":"crossref","award":["NWO-ZonMw: 91216045"],"award-info":[{"award-number":["NWO-ZonMw: 91216045"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,22]]},"abstract":"<jats:p>\n                    Angelman syndrome (AS) is a severe neurodevelopmental disorder (NDD) caused by loss of functional ubiquitin protein ligase E3A (UBE3A). Previous studies showed that UBE3A plays an important role in the first postnatal weeks of mouse brain development, but its precise role is unknown. Since impaired striatal maturation has been implicated in several mouse models for NDDs, we studied the importance of UBE3A in striatal maturation. We used inducible\n                    <jats:italic>Ube3a<\/jats:italic>\n                    mouse models to investigate the maturation of medium spiny neurons (MSNs) from dorsomedial striatum. MSNs of mutant mice matured properly till postnatal day 15 (P15) but remained hyperexcitable with fewer excitatory synaptic events at later ages, indicative of stalled striatal maturation in\n                    <jats:italic>Ube3a<\/jats:italic>\n                    mice. Reinstatement of UBE3A expression at P21 fully restored MSN excitability but only partially restored synaptic transmission and the operant conditioning behavioral phenotype. Gene reinstatement at P70 failed to rescue both electrophysiological and behavioral phenotypes. In contrast, deletion of\n                    <jats:italic>Ube3a<\/jats:italic>\n                    after normal brain development did not result in these electrophysiological and behavioral phenotypes. This study emphasizes the role of UBE3A in striatal maturation and the importance of early postnatal reinstatement of UBE3A expression to obtain a full rescue of behavioral phenotypes associated with striatal function in AS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.166073","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T14:01:08Z","timestamp":1676988068000},"source":"Crossref","is-referenced-by-count":16,"title":["UBE3A expression during early postnatal brain development is required for proper dorsomedial striatal maturation"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-3596","authenticated-orcid":true,"given":"Diana C.","family":"Rotaru","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics and"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Rotterdam, 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