{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:31:49Z","timestamp":1792189909449,"version":"4.4.0"},"reference-count":15,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00247585"],"award-info":[{"award-number":["RS-2023-00247585"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A2B4002683 2018R1A5A2025079 2022M3E5E8018388"],"award-info":[{"award-number":["2017R1A2B4002683 2018R1A5A2025079 2022M3E5E8018388"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C3002354"],"award-info":[{"award-number":["2019R1A2C3002354"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,5,21]]},"abstract":"<jats:p>\n                    Protocadherin19 (\n                    <jats:italic>PCDH19<\/jats:italic>\n                    )-related epilepsy syndrome is a rare disorder characterized by early-onset epilepsy, intellectual disability, and autistic behaviors.\n                    <jats:italic>PCDH19<\/jats:italic>\n                    is located on the X chromosome and encodes a calcium-dependent single-pass transmembrane protein, which regulates cell-to-cell adhesion through homophilic binding. In human, 90% of heterozygous females, containing\n                    <jats:italic>PCDH19<\/jats:italic>\n                    wild-type and mutant cells due to random X inactivation, are affected, whereas mutant males, containing only mutant cells, are typically not. The current view, the cellular interference, is that the altered interactions between wild-type and mutant cells during development, rather than loss of function itself, are responsible. However, studies using\n                    <jats:italic>Pcdh19<\/jats:italic>\n                    knockout mice showed that the complete loss of function also causes autism-like behaviors both in males and females, suggesting that other functions of PCDH19 may also contribute to pathogenesis. To address whether mosaicism is required for\n                    <jats:italic>PCDH19<\/jats:italic>\n                    -related epilepsy, we generated\n                    <jats:italic>Xenopus tropicalis<\/jats:italic>\n                    tadpoles with complete or mosaic loss of function by injecting antisense morpholino oligonucleotides into the blastomeres of neural lineage at different stages of development. We found that either mosaic or complete knockdown results in seizure-like behaviors, which could be rescued by antiseizure medication, and repetitive behaviors. Our results suggest that the loss of PCDH19 function itself, in addition to cellular interference, may also contribute to\n                    <jats:italic>PCDH19<\/jats:italic>\n                    -related epilepsy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2321388121","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T12:47:42Z","timestamp":1715777262000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Mosaicism-independent mechanisms contribute to Pcdh19-related epilepsy and repetitive behaviors in\n                    <i>Xenopus<\/i>"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0219-5335","authenticated-orcid":false,"given":"Jugeon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-429X","authenticated-orcid":false,"given":"Chul Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeon","family":"Ohk","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5059-8050","authenticated-orcid":false,"given":"Hosung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.12.005"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21373"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18529"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-017-0517-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000381"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.06.008"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06374-x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-019-0519-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16675"},{"key":"e_1_3_3_10_2","first-page":"1057","article-title":"Modeling human neurodevelopmental disorders in the Xenopus tadpole: From mechanisms to therapeutic targets","volume":"6","author":"Pratt K. G.","year":"2013","unstructured":"K. G. Pratt, A. S. Khakhalin, Modeling human neurodevelopmental disorders in the Xenopus tadpole: From mechanisms to therapeutic targets. Dis. Model Mech. 6, 1057\u20131065 (2013).","journal-title":"Dis. Model Mech."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25032"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.1042"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2016.01.006"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105738"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02099-7"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2321388121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T09:42:58Z","timestamp":1722246178000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2321388121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":15,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2024,5,21]]}},"alternative-id":["10.1073\/pnas.2321388121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2321388121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"assertion":[{"value":"2023-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2321388121"}}