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In the brain, the phenotypic spectrum of\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    -related segmental overgrowth includes bilateral dysplastic megalencephaly, hemimegalencephaly and focal cortical dysplasia, the most common cause of intractable pediatric epilepsy. We generated mouse models expressing the most common activating\n                    <jats:italic>Pik3ca<\/jats:italic>\n                    mutations (\n                    <jats:italic>H1047R<\/jats:italic>\n                    and\n                    <jats:italic>E545K<\/jats:italic>\n                    ) in developing neural progenitors. These accurately recapitulate all the key human pathological features including brain enlargement, cortical malformation, hydrocephalus and epilepsy, with phenotypic severity dependent on the mutant allele and its time of activation. Underlying mechanisms include increased proliferation, cell size and altered white matter. Notably, we demonstrate that acute 1 hr-suppression of PI3K signaling despite the ongoing presence of dysplasia has dramatic anti-epileptic benefit. Thus PI3K inhibitors offer a promising new avenue for effective anti-epileptic therapy for intractable pediatric epilepsy patients.\n                  <\/jats:p>","DOI":"10.7554\/elife.12703","type":"journal-article","created":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T07:58:46Z","timestamp":1449129526000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.12703","source":"Crossref","is-referenced-by-count":106,"title":["Mouse models of human PIK3CA-related brain overgrowth have acutely treatable epilepsy"],"prefix":"10.7554","volume":"4","author":[{"given":"Achira","family":"Roy","sequence":"first","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Skibo","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Kalume","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana Farber Cancer Institute, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri","family":"Rankin","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Lu","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William 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