{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:24:25Z","timestamp":1793381065745,"version":"4.5.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,12,26]]},"abstract":"<jats:p>\n                    Mutations in the X-linked cyclin-dependent kinase-like 5 (\n                    <jats:italic>CDKL5<\/jats:italic>\n                    ) gene have been identified in neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 and its role in the etiology of these disorders, however, remain unclear. Here we report the development of a unique knockout mouse model of CDKL5-related disorders and demonstrate that mice lacking CDKL5 show autistic-like deficits in social interaction, as well as impairments in motor control and fear memory. Neurophysiological recordings reveal alterations in event-related potentials (ERPs) similar to those observed in RTT and ASDs. Moreover, kinome profiling uncovers disruption of multiple signal transduction pathways, including the AKT-mammalian target of rapamycin (mTOR) cascade, upon\n                    <jats:italic>Cdkl5<\/jats:italic>\n                    loss-of-function. These data demonstrate that CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role for\n                    <jats:italic>Cdkl5<\/jats:italic>\n                    loss-of-function in neurodevelopmental disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1216988110","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T21:28:16Z","timestamp":1355261296000},"page":"21516-21521","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":217,"title":["Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice"],"prefix":"10.1073","volume":"109","author":[{"given":"I-Ting Judy","family":"Wang","sequence":"first","affiliation":[{"name":"Departments of aGenetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Allen","sequence":"additional","affiliation":[{"name":"Departments of aGenetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Goffin","sequence":"additional","affiliation":[{"name":"Departments of aGenetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Neurology,"},{"name":"Division of Child Neurology, Department of Pediatrics and Neurology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Fairless","sequence":"additional","affiliation":[{"name":"Psychiatry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward S.","family":"Brodkin","sequence":"additional","affiliation":[{"name":"Psychiatry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve J.","family":"Siegel","sequence":"additional","affiliation":[{"name":"Psychiatry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Neurology,"},{"name":"Division of Child Neurology, Department of Pediatrics and Neurology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Blendy","sequence":"additional","affiliation":[{"name":"Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of aGenetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,12,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.12"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002166"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.028"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn197"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/728267"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi198"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.10.113"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2566"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1102-10.2010"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi391"},{"key":"e_1_3_3_12_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000331333","article-title":"CDKL5-related disorders: From clinical description to molecular genetics","volume":"2","author":"Bahi-Buisson N","year":"2012","unstructured":"N Bahi-Buisson, T Bienvenu, CDKL5-related disorders: From clinical description to molecular genetics. 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