{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nwosu GI"],"funding":["NINDS NIH HHS"],"pagination":["8458"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10179596"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(9)"],"pubmed_abstract":["Lennox-Gastaut 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 <i>GABRB3</i> that encodes the GABA<sub>A</sub> receptor (GABA<sub>A</sub>R) β<sub>3</sub> subunit. LGS has an unknown pathophysiology, and few animal models are available for studying LGS. The objective of this study was to evaluate <i>Gabrb3</i><sup>+/N328D</sup> knock-in mice as a model for LGS. We generated a heterozygous knock-in mouse expressing <i>Gabrb3</i> (c.A982G, p.N238D), a de novo mutation identified in a patient with LGS. We investigated <i>Gabrb3</i><sup>+/N328D</sup> mice for features of LGS. In 2-4-month-old male and female C57BL/J6 wild-type and <i>Gabrb3</i><sup>+/N328D</sup> mice, we investigated seizure severity using video-monitored EEG, cognitive impairment using a suite of behavioral tests, and profiled GABA<sub>A</sub>R subunit expression by Western blot. <i>Gabrb3</i><sup>+/N328D</sup> mice showed spontaneous seizures and signs of cognitive impairment, including deficits in spatial learning, memory, and locomotion. Moreover, <i>Gabrb3</i><sup>+/N328D</sup> mice showed reduced β<sub>3</sub> subunit expression in the cerebellum, hippocampus, and thalamus. This phenotype of epilepsy and neurological impairment resembles the LGS patient phenotype. We conclude that <i>Gabrb3</i><sup>+/N328D</sup> mice provide a good model for investigating the pathophysiology and therapeutic intervention of LGS and DEEs."],"journal":["International journal of molecular sciences"],"pubmed_title":["GABA<sub>A</sub> Receptor β3 Subunit Mutation N328D Heterozygous Knock-in Mice Have Lennox-Gastaut Syndrome."],"pmcid":["PMC10179596"],"funding_grant_id":["NS082635","NS121718"],"pubmed_authors":["Randhave K","Zavalin K","Biven M","Langer K","Flamm C","Poliquin S","Shen W","Kang JQ","Nwosu GI"],"additional_accession":[]},"is_claimable":false,"name":"GABA<sub>A</sub> Receptor β3 Subunit Mutation N328D Heterozygous Knock-in Mice Have Lennox-Gastaut Syndrome.","description":"Lennox-Gastaut 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 <i>GABRB3</i> that encodes the GABA<sub>A</sub> receptor (GABA<sub>A</sub>R) β<sub>3</sub> subunit. LGS has an unknown pathophysiology, and few animal models are available for studying LGS. The objective of this study was to evaluate <i>Gabrb3</i><sup>+/N328D</sup> knock-in mice as a model for LGS. We generated a heterozygous knock-in mouse expressing <i>Gabrb3</i> (c.A982G, p.N238D), a de novo mutation identified in a patient with LGS. We investigated <i>Gabrb3</i><sup>+/N328D</sup> mice for features of LGS. In 2-4-month-old male and female C57BL/J6 wild-type and <i>Gabrb3</i><sup>+/N328D</sup> mice, we investigated seizure severity using video-monitored EEG, cognitive impairment using a suite of behavioral tests, and profiled GABA<sub>A</sub>R subunit expression by Western blot. <i>Gabrb3</i><sup>+/N328D</sup> mice showed spontaneous seizures and signs of cognitive impairment, including deficits in spatial learning, memory, and locomotion. Moreover, <i>Gabrb3</i><sup>+/N328D</sup> mice showed reduced β<sub>3</sub> subunit expression in the cerebellum, hippocampus, and thalamus. This phenotype of epilepsy and neurological impairment resembles the LGS patient phenotype. We conclude that <i>Gabrb3</i><sup>+/N328D</sup> mice provide a good model for investigating the pathophysiology and therapeutic intervention of LGS and DEEs.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2025-04-05T09:11:17.209Z","creation":"2025-04-05T09:11:17.209Z"},"accession":"S-EPMC10179596","cross_references":{"pubmed":["37176165"],"doi":["10.3390/ijms24098458"]}}