{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:09:09Z","timestamp":1790122149003,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Health (NINDS)","doi-asserted-by":"publisher","award":["NS082635"],"award-info":[{"award-number":["NS082635"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Health (NINDS)","doi-asserted-by":"publisher","award":["NS121718"],"award-info":[{"award-number":["NS121718"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Health (NINDS)","doi-asserted-by":"publisher","award":["5R25GM059994-22"],"award-info":[{"award-number":["5R25GM059994-22"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lennox\u2013Gastaut Syndrome (LGS) is a developmental and epileptic encephalopathy (DEE) characterized by multiple seizure types, electroencephalogram (EEG) patterns, and cognitive decline. Its etiology has a prominent genetic component, including variants in GABRB3 that encodes the GABAA receptor (GABAAR) \u03b23 subunit. LGS has an unknown pathophysiology, and few animal models are available for studying LGS. The objective of this study was to evaluate Gabrb3+\/N328D knock-in mice as a model for LGS. We generated a heterozygous knock-in mouse expressing Gabrb3 (c.A982G, p.N238D), a de novo mutation identified in a patient with LGS. We investigated Gabrb3+\/N328D mice for features of LGS. In 2\u20134-month-old male and female C57BL\/J6 wild-type and Gabrb3+\/N328D mice, we investigated seizure severity using video-monitored EEG, cognitive impairment using a suite of behavioral tests, and profiled GABAAR subunit expression by Western blot. Gabrb3+\/N328D mice showed spontaneous seizures and signs of cognitive impairment, including deficits in spatial learning, memory, and locomotion. Moreover, Gabrb3+\/N328D mice showed reduced \u03b23 subunit expression in the cerebellum, hippocampus, and thalamus. This phenotype of epilepsy and neurological impairment resembles the LGS patient phenotype. We conclude that Gabrb3+\/N328D mice provide a good model for investigating the pathophysiology and therapeutic intervention of LGS and DEEs.<\/jats:p>","DOI":"10.3390\/ijms24098458","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T02:28:08Z","timestamp":1683599288000},"page":"8458","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["GABAA Receptor \u03b23 Subunit Mutation N328D Heterozygous Knock-in Mice Have Lennox\u2013Gastaut Syndrome"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6697-0585","authenticated-orcid":false,"given":"Gerald Ikemefuna","family":"Nwosu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Graduate Studies, Meharry Medical College, Nashville, TN 37208, USA"},{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangzhen","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Zavalin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4151-3991","authenticated-orcid":false,"given":"Sarah","family":"Poliquin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karishma","family":"Randhave","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6070-0864","authenticated-orcid":false,"given":"Carson","family":"Flamm","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Biven","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Langer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"},{"name":"Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Qiong","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt Brain Institute, Nashville, TN 37232, USA"},{"name":"Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"ref_1","first-page":"403","article-title":"Lennox-Gastaut syndrome: A comprehensive review","volume":"39","year":"2017","journal-title":"Neurol. 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