{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T19:52:53Z","timestamp":1776023573127,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,22]]},"group-title":"Neuroscience","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,22]]},"abstract":"<jats:title>Abstracts<\/jats:title>\n                <jats:p>\n                  Single allelic mutations in the forebrain-specific transcription factor gene\n                  <jats:italic>FOXG1<\/jats:italic>\n                  lead to FOXG1 syndrome (FS). To decipher the disease mechanisms of FS, which vary depending on FOXG1 mutation types, patient-specific animal models are critical. Here, we report the first patient-specific FS mouse model,\n                  <jats:italic>Q84Pfs<\/jats:italic>\n                  heterozygous (Q84Pfs-Het) mice, which emulates one of the most predominant FS variants. Remarkably, Q84Pfs-Het mice recapitulate various human FS phenotypes across cellular, brain structural, and behavioral levels, such as microcephaly, corpus callosum agenesis, movement disorders, repetitive behaviors, and anxiety. Q84Pfs-Het cortex showed dysregulations of genes controlling cell proliferation, neuronal projection and migration, synaptic assembly, and synaptic vesicle transport. Interestingly, the FS-causing\n                  <jats:italic>Q84Pfs<\/jats:italic>\n                  allele produced the N-terminal fragment of FOXG1, denoted as Q84Pfs protein, in Q84Pfs-Het mouse brains. Q84Pfs fragment forms intracellular speckles, interacts with FOXG1 full-length protein, and triggers the sequestration of FOXG1 to distinct subcellular domains. Q84Pfs protein also promotes the radial glial cell identity and suppresses neuronal migration in the cortex. Together, our study uncovered the role of the FOXG1 fragment derived from FS-causing\n                  <jats:italic>FOXG1<\/jats:italic>\n                  variants and identified the genes involved in FS-like cellular and behavioral phenotypes, providing essential insights into the pathophysiology of FS.\n                <\/jats:p>","DOI":"10.1101\/2025.01.21.634140","type":"posted-content","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T07:41:11Z","timestamp":1737531671000},"source":"Crossref","is-referenced-by-count":2,"title":["The patient-specific mouse model with\n                  <i>Foxg1<\/i>\n                  frameshift mutation provides insights into the pathophysiology of FOXG1 syndrome"],"prefix":"10.64898","author":[{"given":"Shin","family":"Jeon","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"},{"name":"Department of Systems Pharmacology & Translational Therapeutics, University of Pennsylvania, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaein","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hwan","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"},{"name":"Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongjun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon Ung","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyo-Jong","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Brimble","sequence":"additional","affiliation":[{"name":"Invitae, Corp, San Francisco, California, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stewart","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo-Kyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences"},{"name":"FOXG1 Research Center, University at Buffalo, Buffalo, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041022250816000_2025.01.21.634140v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90210-5"},{"key":"2026041022250816000_2025.01.21.634140v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90262-7"},{"key":"2026041022250816000_2025.01.21.634140v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.07.009"},{"key":"2026041022250816000_2025.01.21.634140v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.009"},{"key":"2026041022250816000_2025.01.21.634140v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.04.005"},{"key":"2026041022250816000_2025.01.21.634140v1.6","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-6-9"},{"key":"2026041022250816000_2025.01.21.634140v1.7","doi-asserted-by":"publisher","DOI":"10.1242\/dev.039800"},{"key":"2026041022250816000_2025.01.21.634140v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090674"},{"key":"2026041022250816000_2025.01.21.634140v1.9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06526.2002"},{"key":"2026041022250816000_2025.01.21.634140v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.025"},{"key":"2026041022250816000_2025.01.21.634140v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.016"},{"key":"2026041022250816000_2025.01.21.634140v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.02.023"},{"key":"2026041022250816000_2025.01.21.634140v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11043-w"},{"key":"2026041022250816000_2025.01.21.634140v1.14","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh3568"},{"key":"2026041022250816000_2025.01.21.634140v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23987-z"},{"key":"2026041022250816000_2025.01.21.634140v1.16","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy051"},{"key":"2026041022250816000_2025.01.21.634140v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.01.002"},{"key":"2026041022250816000_2025.01.21.634140v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2021.104282"},{"key":"2026041022250816000_2025.01.21.634140v1.19","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000281"},{"key":"2026041022250816000_2025.01.21.634140v1.20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174176"},{"key":"2026041022250816000_2025.01.21.634140v1.21","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.087528"},{"key":"2026041022250816000_2025.01.21.634140v1.22","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12894"},{"key":"2026041022250816000_2025.01.21.634140v1.23","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002585"},{"key":"2026041022250816000_2025.01.21.634140v1.24","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-4949811\/v1"},{"key":"2026041022250816000_2025.01.21.634140v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.75"},{"key":"2026041022250816000_2025.01.21.634140v1.26","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9732"},{"key":"2026041022250816000_2025.01.21.634140v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.06.012"},{"key":"2026041022250816000_2025.01.21.634140v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.07.007"},{"key":"2026041022250816000_2025.01.21.634140v1.29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.2010.02307.x"},{"key":"2026041022250816000_2025.01.21.634140v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1155"},{"key":"2026041022250816000_2025.01.21.634140v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"2026041022250816000_2025.01.21.634140v1.32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2122467120"},{"key":"2026041022250816000_2025.01.21.634140v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"2026041022250816000_2025.01.21.634140v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"2026041022250816000_2025.01.21.634140v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.05.015"},{"key":"2026041022250816000_2025.01.21.634140v1.36","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x16666180302115032"},{"key":"2026041022250816000_2025.01.21.634140v1.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049838"},{"key":"2026041022250816000_2025.01.21.634140v1.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818042116"},{"key":"2026041022250816000_2025.01.21.634140v1.39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0266861"},{"key":"2026041022250816000_2025.01.21.634140v1.40","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.927296"},{"key":"2026041022250816000_2025.01.21.634140v1.41","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhm209"},{"key":"2026041022250816000_2025.01.21.634140v1.42","doi-asserted-by":"publisher","DOI":"10.1159\/000330213"},{"key":"2026041022250816000_2025.01.21.634140v1.43","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00132"},{"key":"2026041022250816000_2025.01.21.634140v1.44","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22657"},{"key":"2026041022250816000_2025.01.21.634140v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2006.04.017"},{"key":"2026041022250816000_2025.01.21.634140v1.46","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2021-244206"},{"key":"2026041022250816000_2025.01.21.634140v1.47","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23524"},{"key":"2026041022250816000_2025.01.21.634140v1.48","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33785"},{"key":"2026041022250816000_2025.01.21.634140v1.49","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.58.6.962"},{"key":"2026041022250816000_2025.01.21.634140v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.008"},{"key":"2026041022250816000_2025.01.21.634140v1.51","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws205"},{"key":"2026041022250816000_2025.01.21.634140v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.12.017"},{"key":"2026041022250816000_2025.01.21.634140v1.53","unstructured":"Kumar, A. & Sharma, S. in StatPearls (StatPearls Publishing Copyright \u00a9 2023, StatPearls Publishing LLC., 2023)."},{"key":"2026041022250816000_2025.01.21.634140v1.54","doi-asserted-by":"publisher","DOI":"10.1177\/15357597211029507"},{"key":"2026041022250816000_2025.01.21.634140v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.10.010"},{"key":"2026041022250816000_2025.01.21.634140v1.56","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-017-0758-6"},{"key":"2026041022250816000_2025.01.21.634140v1.57","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12648"},{"key":"2026041022250816000_2025.01.21.634140v1.58","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/9.6.543"},{"key":"2026041022250816000_2025.01.21.634140v1.59","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.6.1303"},{"key":"2026041022250816000_2025.01.21.634140v1.60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030080"},{"key":"2026041022250816000_2025.01.21.634140v1.61","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34177"},{"key":"2026041022250816000_2025.01.21.634140v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.10.006"},{"key":"2026041022250816000_2025.01.21.634140v1.63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515190112"},{"key":"2026041022250816000_2025.01.21.634140v1.64","doi-asserted-by":"publisher","DOI":"10.1002\/stem.443"},{"key":"2026041022250816000_2025.01.21.634140v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3390"},{"key":"2026041022250816000_2025.01.21.634140v1.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.04.001"},{"key":"2026041022250816000_2025.01.21.634140v1.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2024.101275"},{"key":"2026041022250816000_2025.01.21.634140v1.68","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-021-04344-9"},{"key":"2026041022250816000_2025.01.21.634140v1.69","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-0994-9"},{"key":"2026041022250816000_2025.01.21.634140v1.70","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026041022250816000_2025.01.21.634140v1.71","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"2026041022250816000_2025.01.21.634140v1.72","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt087"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.01.21.634140","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:25:16Z","timestamp":1775885116000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.01.21.634140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":72,"URL":"https:\/\/doi.org\/10.1101\/2025.01.21.634140","relation":{},"subject":[],"published":{"date-parts":[[2025,1,22]]},"subtype":"preprint"}}