{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:12Z","timestamp":1787028612804,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL134599-05"],"award-info":[{"award-number":["P01 HL134599-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL145060-03"],"award-info":[{"award-number":["R01 HL145060-03"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01HL148165"],"award-info":[{"award-number":["5R01HL148165"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"generosity of the Riley Children\u2019s Foundation","award":["P01 HL134599-05"],"award-info":[{"award-number":["P01 HL134599-05"]}]},{"name":"generosity of the Riley Children\u2019s Foundation","award":["R01 HL145060-03"],"award-info":[{"award-number":["R01 HL145060-03"]}]},{"name":"generosity of the Riley Children\u2019s Foundation","award":["5R01HL148165"],"award-info":[{"award-number":["5R01HL148165"]}]},{"name":"Division of Pediatric Cardiology","award":["P01 HL134599-05"],"award-info":[{"award-number":["P01 HL134599-05"]}]},{"name":"Division of Pediatric Cardiology","award":["R01 HL145060-03"],"award-info":[{"award-number":["R01 HL145060-03"]}]},{"name":"Division of Pediatric Cardiology","award":["5R01HL148165"],"award-info":[{"award-number":["5R01HL148165"]}]},{"name":"Carleton Buehl McCulloch Chair of Pediatrics","award":["P01 HL134599-05"],"award-info":[{"award-number":["P01 HL134599-05"]}]},{"name":"Carleton Buehl McCulloch Chair of Pediatrics","award":["R01 HL145060-03"],"award-info":[{"award-number":["R01 HL145060-03"]}]},{"name":"Carleton Buehl McCulloch Chair of Pediatrics","award":["5R01HL148165"],"award-info":[{"award-number":["5R01HL148165"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>The cardiac conduction system, a network of specialized cells, is required for the functioning of the heart. The basic helix loop helix factors Hand1 and Hand2 are required for cardiac morphogenesis and have been implicated in cardiac conduction system development and maintenance. Here we use embryonic and post-natal specific Cre lines to interrogate the role of Hand1 and Hand2 in the function of the murine cardiac conduction system. Results demonstrate that loss of HAND1 in the post-natal conduction system does not result in any change in electrocardiogram parameters or within the ventricular conduction system as determined by optical voltage mapping. Deletion of Hand2 within the post-natal conduction system results in sex-dependent reduction in PR interval duration in these mice, suggesting a novel role for HAND2 in regulating the atrioventricular conduction. Surprisingly, results show that loss of both HAND factors within the post-natal conduction system does not cause any consistent changes in cardiac conduction system function. Deletion of Hand2 in the embryonic left ventricle results in inconsistent prolongation of PR interval and susceptibility to atrial arrhythmias. Thus, these results suggest a novel role for HAND2 in homeostasis of the murine cardiac conduction system and that HAND1 loss potentially rescues the shortened HAND2 PR phenotype.<\/jats:p>","DOI":"10.3390\/jcdd9070214","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T11:15:05Z","timestamp":1656933305000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neonatal Deletion of Hand1 and Hand2 within Murine Cardiac Conduction System Reveals a Novel Role for HAND2 in Rhythm Homeostasis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-5523","authenticated-orcid":false,"given":"Rajani M.","family":"George","sequence":"first","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Departments of Pediatrics, Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, The Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Firulli","sequence":"additional","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Departments of Pediatrics, Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7386-6943","authenticated-orcid":false,"given":"Michael","family":"Rubart","sequence":"additional","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Departments of Pediatrics, Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, IN 46202, USA"},{"name":"Division of Cardiology, Department of Medicine, The Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6687-8949","authenticated-orcid":false,"given":"Anthony B.","family":"Firulli","sequence":"additional","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Departments of Pediatrics, Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/pace.14107","article-title":"Anatomy of the cardiac conduction system","volume":"44","author":"Padala","year":"2021","journal-title":"Pacing Clin. 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