{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:05:55Z","timestamp":1790744755815,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201014\u2010CE13\u20100011"],"award-info":[{"award-number":["ANR\u201014\u2010CE13\u20100011"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201019\u2010CE17\u20100018"],"award-info":[{"award-number":["ANR\u201019\u2010CE17\u20100018"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007586","name":"Aix-Marseille Universit\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Early onset epileptic encephalopathy with suppression\u2010burst is one of the most severe epilepsy phenotypes in human patients. A significant proportion of cases have a genetic origin, and the most frequently mutated gene is <jats:italic>KCNQ2<\/jats:italic>, encoding Kv7.2, a voltage\u2010dependent potassium channel subunit, leading to so\u2010called <jats:italic>KCNQ2<\/jats:italic>\u2010related epileptic encephalopathy (<jats:italic>KCNQ2<\/jats:italic>\u2010REE). To study the pathophysiology of <jats:italic>KCNQ2<\/jats:italic>\u2010REE in detail and to provide a relevant preclinical model, we generated and described a knock\u2010in mouse model carrying the recurrent p.(Thr274Met) variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We introduced the p.(Thr274Met) variant by homologous recombination in embryonic stem cells, injected into C57Bl\/6N blastocysts and implanted in pseudopregnant mice. Mice were then bred with 129Sv Cre\u2010deleter to generate heterozygous mice carrying the p.(Thr274Met), and animals were maintained on the 129Sv genetic background. We studied the development of this new model and performed in vivo electroencephalographic (EEG) recordings, neuroanatomical studies at different time points, and multiple behavioral tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>Kcnq2<\/jats:italic><jats:sup>Thr274Met\/+<\/jats:sup> mice are viable and display generalized spontaneous seizures first observed between postnatal day 20 (P20) and P30. In vivo EEG recordings show that the paroxysmal events observed macroscopically are epileptic seizures. The brain of the <jats:italic>Kcnq2<\/jats:italic><jats:sup>Thr274Met\/+<\/jats:sup> animals does not display major structural defects, similar to humans, and their body weight is normal. <jats:italic>Kcnq2<\/jats:italic><jats:sup>Thr274Met\/+<\/jats:sup> mice have a reduced life span, with a peak of unexpected death occurring for 25% of the animals by 3\u00a0months of age. Epileptic seizures were generally not observed when animals grew older. Behavioral characterization reveals important deficits in spatial learning and memory in adults but no gross abnormality during early neurosensory development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Taken together, our results indicate that we have generated a relevant model to study the pathophysiology of <jats:italic>KCNQ2<\/jats:italic>\u2010related epileptic encephalopathy and perform preclinical research for that devastating and currently intractable disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16494","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T11:37:41Z","timestamp":1585827461000},"page":"868-878","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["A knock\u2010in mouse model for <i>KCNQ2<\/i>\u2010related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-8543","authenticated-orcid":false,"given":"Mathieu","family":"Milh","sequence":"first","affiliation":[{"name":"Aix Marseille Univ Inserm, MMG Marseille France"},{"name":"Department of Pediatric Neurology La Timone Children's Hospital Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9013-2725","authenticated-orcid":false,"given":"Pierre","family":"Roubertoux","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ Inserm, MMG Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najoua","family":"Biba","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille University, Inmed, Inserm, U1249 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Chavany","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ Inserm, MMG 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