{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:27:28Z","timestamp":1761560848976},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,10,13]],"date-time":"2003-10-13T00:00:00Z","timestamp":1066003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nkx2.5 is a conserved homeodomain (HD) containing a transcription factor essential for early cardiac development. We generated several mutations modeling some patients with congenital heart disease. Transgenic mice (tg) expressing the wildtype Nkx2.5 under \u03b2\u2010myosin heavy chain (MHC) promoter died during the embryonic stage. However, tg mice expressing this mutation under \u03b2\u2010MHC promoter (\u03b2\u2010MHC\u2010TG(I183P)), the wildtype Nkx2.5 (\u03b1\u2010MHC\u2010TG(wild)), and a putative transcriptionally active mutant (carboxyl\u2010terminus deletion, \u03b1\u2010MHC\u2010TG(\u0394C)) under \u03b1\u2010MHC promoter showed postnatal lethal heart failure. Given the profound atrioventricular conduction abnormalities we recently demonstrated in \u03b2\u2010MHC\u2010TG(I183P) mice, the aim of this study was to determine whether \u03b1\u2010MHC\u2010TG(wild) and \u03b1\u2010MHC\u2010TG(\u0394C) mutant mice display similar cardiac electrophysiological phenotypes. Surface ECG recordings and in vivo electrophysiology studies were performed in \u03b1\u2010MHC\u2010TG(wild) mice and controls at 6 weeks of age, and in \u03b1\u2010MHC\u2010TG(\u0394C) mice and controls at 10 weeks of age. Ambulatory ECG recordings in \u03b1\u2010MHC\u2010TG(wild) and controls were obtained using an implantable radiofrequency telemetry system. PR prolongation and atrioventricular nodal dysfunction were detected in \u03b1\u2010MHC\u2010TG(wild) and \u03b1\u2010MHC\u2010TG(\u0394C) mice. Bradycardia and prolonged PR interval were seen in ambulatory ECG of \u03b1\u2010MHC\u2010TG(wild) mice compared to controls. Several \u03b1\u2010MHC\u2010TG(wild) mice died of bradycardia. Fetal and neonatal mutant Nkx2.5 expression causes severe cardiac conduction failure. Postnatal overexpression of nonmutant (wild) Nkx2.5 also causes conduction abnormalities, although the onset is after the neonatal stage. Bradycardia and AV conduction failure may contribute to the lethal heart failure and early mortality. genesis 37:144\u2013150, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gene.10236","type":"journal-article","created":{"date-parts":[[2003,10,29]],"date-time":"2003-10-29T10:00:32Z","timestamp":1067421632000},"page":"144-150","source":"Crossref","is-referenced-by-count":11,"title":["Cardiac electrophysiological phenotypes in postnatal expression of Nkx2.5 transgenic mice"],"prefix":"10.1002","volume":"37","author":[{"given":"Hiroko","family":"Wakimoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideko","family":"Kasahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin T.","family":"Maguire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan P.G.","family":"Moskowitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seigo","family":"Izumo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles I.","family":"Berul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,10,13]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1996.tb00466.x"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8154"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.10.2641"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119197"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1009800328836"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.26.15628"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.2.H733"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4601.098427"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119367"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31568-0"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9041"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.11.1508"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.1.526"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.9.936"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9860"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12694"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00002-6"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70114-9"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.5.399"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.8145"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.6.3120"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.119.2.419"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.5.346"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1654"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2000.tb00009.x"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.05.004"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.3.H747"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7892609"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5373.108"},{"key":"e_1_2_1_31_1","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1242\/dev.126.6.1269","article-title":"The cardiac homeobox gene Nkx2.5 lies genetically upstream of multiple genes essential for heart development","volume":"126","author":"Tanaka M","year":"1999","journal-title":"Development"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2002.67.317"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.7.686"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1101.091107"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.11.1591"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00264-4"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1540-8167.2002.00682.x"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.11.807"}],"container-title":["genesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgene.10236","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gene.10236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:04:33Z","timestamp":1700179473000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gene.10236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,13]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,11]]}},"alternative-id":["10.1002\/gene.10236"],"URL":"https:\/\/doi.org\/10.1002\/gene.10236","archive":["Portico"],"relation":{},"ISSN":["1526-954X","1526-968X"],"issn-type":[{"value":"1526-954X","type":"print"},{"value":"1526-968X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10,13]]}}}