{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:39:57Z","timestamp":1792017597620,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R00 NS089943"],"award-info":[{"award-number":["R00 NS089943"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>PCDH19<\/jats:italic>\n                      \u2010related epilepsy is characterized by a distinctive pattern of X\u2010linked inheritance, where heterozygous females exhibit seizures and hemizygous males are asymptomatic. A cellular interference mechanism resulting from the presence of both wild\u2010type and mutant PCDH19 neurons in heterozygous patients or mosaic carriers of\n                      <jats:italic>PCDH19<\/jats:italic>\n                      variants has been hypothesized. We aim to investigate seizure susceptibility and progression in the\n                      <jats:italic>Pchd19<\/jats:italic>\n                      mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We assessed seizure susceptibility and progression in the\n                      <jats:italic>Pcdh19<\/jats:italic>\n                      mouse model using three acute seizure induction paradigms. We first induced focal, clonic seizures using the 6\u2010Hz psychomotor test. Mice were stimulated with increasing current intensities and graded according to a modified Racine scale. We next induced generalized seizures using flurothyl or pentylenetetrazol (PTZ), both \u03b3\u2010aminobutyric acid type A receptor function inhibitors, and recorded latencies to myoclonic and generalized tonic\u2010clonic seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pcdh19<\/jats:italic>\n                      knockout and heterozygous females displayed increased seizure susceptibility across all current intensities in the 6\u2010Hz psychomotor test, and increased severity overall. They also exhibited shorter latencies to generalized seizures following flurothyl, but not PTZ, seizure induction. Hemizygous males showed comparable seizure incidence and severity to their wild\u2010type male littermates across all paradigms tested.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      The heightened susceptibility observed in\n                      <jats:italic>Pcdh19<\/jats:italic>\n                      knockout females suggests additional mechanisms other than cellular interference are at play in\n                      <jats:italic>PCDH19<\/jats:italic>\n                      \u2010related epilepsy. Further experiments are needed to understand the variability in seizure susceptibility so that this model can be best utilized toward development of future therapeutic strategies for\n                      <jats:italic>PCDH19<\/jats:italic>\n                      \u2010related epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.16675","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T03:37:13Z","timestamp":1600400233000},"page":"2313-2320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Characterization of seizure susceptibility in\n                    <i>Pcdh19<\/i>\n                    mice"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6375-0920","authenticated-orcid":false,"given":"Jennifer","family":"Rakotomamonjy","sequence":"first","affiliation":[{"name":"Department of Physiology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki P.","family":"Sabetfakhri","sequence":"additional","affiliation":[{"name":"Department of Physiology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean L.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Physiology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-4661","authenticated-orcid":false,"given":"Alicia","family":"Guemez\u2010Gamboa","sequence":"additional","affiliation":[{"name":"Department of Physiology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.149"},{"issue":"75","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1212\/WNL.0b013e3181ed9e67","article-title":"Protocadherin 19 mutations in girls with infantile\u2010onset epilepsy","volume":"17","author":"Marini 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