{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:47:31Z","timestamp":1793144851848,"version":"4.5.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,4]]},"abstract":"<jats:p>\n                    Heterozygous loss-of-function mutations in the brain sodium channel Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 cause Dravet syndrome (DS), a pharmacoresistant infantile-onset epilepsy syndrome with comorbidities of cognitive impairment and premature death. Previous studies using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic interneurons in the hippocampus, leading to the hypothesis that impaired excitability of GABAergic inhibitory neurons is the cause of epilepsy and premature death in DS. However, other classes of GABAergic interneurons are less impaired, so the direct cause of hyperexcitability, epilepsy, and premature death has remained unresolved. We generated a floxed\n                    <jats:italic>Scn1a<\/jats:italic>\n                    mouse line and used the Cre-Lox method driven by an enhancer from the\n                    <jats:italic>Dlx<\/jats:italic>\n                    1,2 locus for conditional deletion of\n                    <jats:italic>Scn1a<\/jats:italic>\n                    in forebrain GABAergic neurons. Immunocytochemical studies demonstrated selective loss of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 channels in GABAergic interneurons in cerebral cortex and hippocampus. Mice with this deletion died prematurely following generalized tonic-clonic seizures, and they were equally susceptible to thermal induction of seizures as mice with global deletion of\n                    <jats:italic>Scn1a<\/jats:italic>\n                    . Evidently, loss of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 channels in forebrain GABAergic neurons is both necessary and sufficient to cause epilepsy and premature death in DS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1211591109","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T00:30:12Z","timestamp":1345509012000},"page":"14646-14651","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":329,"title":["Specific deletion of Na\n                    <sub>V<\/sub>\n                    1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome"],"prefix":"10.1073","volume":"109","author":[{"given":"Christine S.","family":"Cheah","sequence":"first","affiliation":[{"name":"Department of Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank H.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and"},{"name":"Program in Neurobiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Republic of Korea; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth E.","family":"Westenbroek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck K.","family":"Kalume","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Oakley","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Washington, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory B.","family":"Potter","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Rubenstein","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Catterall","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81133-2"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/107385840100700108"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90238-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990920)412:2<342::AID-CNE11>3.0.CO;2-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2532004re15"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.66.032102.113328"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3901-08.2008"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.187484"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.188482"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/320609"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(03)00084-6"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03346.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.02994.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1754"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813330106"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2162-07.2007"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5270-06.2007"},{"key":"e_1_3_3_18_2","first-page":"15","article-title":"Reduced excitability of GABAergic interneurons in the reticular nucleus of the thalamus and sleep impairment in a mouse model of Severe Myoclonic Epilepsy of Infancy","volume":"255","author":"Kalume F","year":"2010","unstructured":"F Kalume, JC Oakley, RE Westenbroek, T Scheuer, WA Catterall, Reduced excitability of GABAergic interneurons in the reticular nucleus of the thalamus and sleep impairment in a mouse model of Severe Myoclonic Epilepsy of Infancy. 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