{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:57:33Z","timestamp":1790701053617,"version":"4.1.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NHLBI Division of Intramural Research","award":["HL169511"],"award-info":[{"award-number":["HL169511"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL171574"],"award-info":[{"award-number":["HL171574"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL127717"],"award-info":[{"award-number":["HL127717"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL118761"],"award-info":[{"award-number":["HL118761"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL136389"],"award-info":[{"award-number":["HL136389"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL163277"],"award-info":[{"award-number":["HL163277"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL164838"],"award-info":[{"award-number":["HL164838"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL166557"],"award-info":[{"award-number":["HL166557"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["DK132286"],"award-info":[{"award-number":["DK132286"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL169742"],"award-info":[{"award-number":["HL169742"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL156465"],"award-info":[{"award-number":["HL156465"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Heart Association","award":["25POST1373848"],"award-info":[{"award-number":["25POST1373848"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Cancer Prevention and Research Institute of Texas","award":["RP210043"],"award-info":[{"award-number":["RP210043"]}],"id":[{"id":"https:\/\/ror.org\/0003xa228","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Atrial fibrillation (AF) is the most common sustained human cardiac arrhythmia and linked to a drastic increase in stroke and heart failure risk. While sequence variations in the\n                    <jats:italic>PITX2<\/jats:italic>\n                    non-coding region are the strongest genetic signature of AF risk, the direct role of PITX2 in AF remains a topic of debate. Here, we generated a mouse model (\n                    <jats:italic>\n                      Pitx2\n                      <jats:sup>Pro41Ser<\/jats:sup>\n                    <\/jats:italic>\n                    ) of a human\n                    <jats:italic>PITX2<\/jats:italic>\n                    coding variant linked to increased AF risk in the Finnish population. The\n                    <jats:italic>\n                      Pitx2\n                      <jats:sup>Pro41Ser<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibit near-complete penetrance of pacing-induced AF, and transcriptional profiling indicates that\n                    <jats:italic>\n                      Pitx2\n                      <jats:sup>Pro41Ser<\/jats:sup>\n                    <\/jats:italic>\n                    is a loss-of-function mutation. In vivo cleavage under targets and tagmentation (CUT&amp;Tag) reveals that PITX2 acts as a transcriptional repressor in developing left atrial cardiomyocytes independent of DNA methylation. Ectopic\n                    <jats:italic>Pitx2<\/jats:italic>\n                    expression in postnatal right atrial cardiomyocytes via adeno-associated virus (AAV) delivery or genetic overexpression represses right atrial genes and induces a left atrial transcriptome, revealing unexpected plasticity of postnatal atrial cardiomyocytes. Strikingly, delivery of\n                    <jats:italic>Pitx2<\/jats:italic>\n                    AAV into\n                    <jats:italic>\n                      Pitx2\n                      <jats:sup>Pro41Ser<\/jats:sup>\n                    <\/jats:italic>\n                    mice rescues AF inducibility uncovering a direct link between PITX2 activity and AF susceptibility.\n                  <\/jats:p>","DOI":"10.1172\/jci207010","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:00:15Z","timestamp":1790697615000},"source":"Crossref","is-referenced-by-count":0,"title":["PITX2 missense coding variant expression in mice reveals direct function in atrial fibrillation"],"prefix":"10.1172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1369-9661","authenticated-orcid":true,"given":"Jeffrey D.","family":"Steimle","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology and The Texas Heart Institute, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohai","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology, Texas A&M University, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati, Cincinnati, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fansen","family":"Meng","sequence":"additional","affiliation":[{"name":"Cardiomyocyte Renewal Laboratory, Texas Heart Institute, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taotao","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and The Texas Heart Institute, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7472-1156","authenticated-orcid":true,"given":"Md. Abul Hassan","family":"Samee","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and The Texas Heart Institute, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology, Texas A&M University, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7842-9857","authenticated-orcid":true,"given":"James F.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and The Texas Heart Institute, Baylor College of Medicine, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,29]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/207010\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:00:17Z","timestamp":1790697617000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/207010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":0,"alternative-id":["10.1172\/JCI207010"],"URL":"https:\/\/doi.org\/10.1172\/jci207010","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}