{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:27:15Z","timestamp":1787725635800,"version":"build-2784847793"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001742","name":"U.S.-Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["#2019065"],"award-info":[{"award-number":["#2019065"]}],"id":[{"id":"10.13039\/501100001742","id-type":"DOI","asserted-by":"publisher"}]},{"name":"GRIN2D Project Foundation"},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["214\/22"],"award-info":[{"award-number":["214\/22"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tel Aviv University Prajs-Drimmer Institute for Development of Anti-Degenerative Drugs"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21-NS121980"],"award-info":[{"award-number":["R21-NS121980"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01-NS031348"],"award-info":[{"award-number":["R01-NS031348"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["U54-OD020351"],"award-info":[{"award-number":["U54-OD020351"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pathogenic variants in GRIN2D, encoding one of the subunits of the N-methyl-D-aspartate receptor (NMDAR), are associated with developmental and epileptic encephalopathies (DEEs). Unusual for de novo mutations, the recurrent, de novo, gain of function, missense mutation c.1999G&amp;gt;A (p.Val667Ile) was discovered in multiple patients.<\/jats:p>\n                  <jats:p>We characterized a mouse model carrying the orthologous Grin2d mutation, using behavioural paradigms, electrophysiological recordings in acute brain slices focusing mainly on the activity of Purkinje neurons in the cerebellum, and electrocorticography (ECoG) recordings monitoring brain activity and the response to several drugs.<\/jats:p>\n                  <jats:p>Grin2d mutant mice exhibit a range of phenotypes that closely mirror the human disease, including premature mortality, spontaneous seizures and early onset of motor deficits followed by cognitive impairment. In addition, we observed complex developmental changes in Purkinje neurons with reduced spontaneous firing in immature mice and augmented synaptic response to NMDA application in older mice. ECoG recordings demonstrated profound and continuous abnormal brain activity, with altered spectral properties and a prominent narrowband activity in the theta, alpha and beta bands, paralleling the patterns seen in a patient with the same GRIN2D pathogenic variant. Acute administration of ketamine at a low dose (0.5\u2005mg\/kg) had a limited effect on the spectral properties, and higher dosages (4 or 10\u2005mg\/kg) caused seizures. Conversely, memantine (10\u2005mg\/kg) and phenytoin (30\u2005mg\/kg) demonstrated a small corrective effect on ECoG properties.<\/jats:p>\n                  <jats:p>Together, Grin2d mutant mice recapitulate key phenotypes of patients with pathogenic GRIN2D variants, including unique, abnormal brain oscillations, which may serve as a biomarker for quantifying drug responses and guiding future research efforts.<\/jats:p>","DOI":"10.1093\/brain\/awaf149","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T07:55:04Z","timestamp":1745394904000},"page":"90-104","source":"Crossref","is-referenced-by-count":6,"title":["A mouse model of\n                    <i>GRIN2D<\/i>\n                    developmental and epileptic encephalopathy recapitulates the human disease"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9534-8037","authenticated-orcid":false,"given":"Mor","family":"Yam","sequence":"first","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry and Goldschleger Eye Research Institute, Gray Faculty of Medical & Health Sciences, Tel Aviv University , Tel Aviv 6139001 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7718-6376","authenticated-orcid":false,"given":"Jolan","family":"Nassir","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry and Goldschleger Eye Research Institute, Gray Faculty of Medical & Health Sciences, Tel Aviv University , Tel Aviv 6139001 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4664-3994","authenticated-orcid":false,"given":"Danielle","family":"Galber","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Gray Faculty of Medical & Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-5535","authenticated-orcid":false,"given":"Shir","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry and Goldschleger Eye Research Institute, Gray Faculty of Medical & Health Sciences, Tel Aviv University , Tel Aviv 6139001 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Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8020-3176","authenticated-orcid":false,"given":"Eden","family":"Peled","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Gray Faculty of Medical & Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1427-8148","authenticated-orcid":false,"given":"Christopher D","family":"Makinson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University Irving Medical Center , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neuroscience, Columbia University Irving Medical Center , New York, NY 10032 ,","place":["USA"]},{"name":"Center for Translational Research in Neurodevelopmental Disease, Columbia University Irving 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