{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:41:34Z","timestamp":1789155694263,"version":"build-2803163510"},"reference-count":93,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["ZIAHD001804"],"award-info":[{"award-number":["ZIAHD001804"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["ZIA HL006247"],"award-info":[{"award-number":["ZIA HL006247"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,8,4]]},"abstract":"<jats:p>\n                    Maternal loss of imprinting (LOI) at the\n                    <jats:italic>H19\/IGF2<\/jats:italic>\n                    locus results in biallelic\n                    <jats:italic>IGF2<\/jats:italic>\n                    and reduced\n                    <jats:italic>H19<\/jats:italic>\n                    expression and is associated with Beckwith\u2013-Wiedemann syndrome (BWS). We use mouse models for LOI to understand the relative importance of\n                    <jats:italic>Igf2<\/jats:italic>\n                    and\n                    <jats:italic>H19<\/jats:italic>\n                    mis-expression in BWS phenotypes. Here we focus on cardiovascular phenotypes and show that neonatal cardiomegaly is exclusively dependent on increased\n                    <jats:italic>Igf2<\/jats:italic>\n                    . Circulating IGF2 binds cardiomyocyte receptors to hyperactivate mTOR signaling, resulting in cellular hyperplasia and hypertrophy. These\n                    <jats:italic>Igf2<\/jats:italic>\n                    -dependent phenotypes are transient: cardiac size returns to normal once\n                    <jats:italic>Igf2<\/jats:italic>\n                    expression is suppressed postnatally. However, reduced\n                    <jats:italic>H19<\/jats:italic>\n                    expression is sufficient to cause progressive heart pathologies including fibrosis and reduced ventricular function. In the heart,\n                    <jats:italic>H19<\/jats:italic>\n                    expression is primarily in endothelial cells (ECs) and regulates EC differentiation both in vivo and in vitro. Finally, we establish novel mouse models to show that cardiac phenotypes depend on\n                    <jats:italic>H19<\/jats:italic>\n                    lncRNA interactions with\n                    <jats:italic>Mirlet7<\/jats:italic>\n                    microRNAs.\n                  <\/jats:p>","DOI":"10.7554\/elife.67250","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T08:00:29Z","timestamp":1629187229000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67250","source":"Crossref","is-referenced-by-count":15,"title":["Cardiac pathologies in mouse loss of imprinting models are due to misexpression of H19 long noncoding RNA"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1322-767X","authenticated-orcid":true,"given":"Ki-Sun","family":"Park","sequence":"first","affiliation":[{"name":"Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-2356","authenticated-orcid":true,"given":"Beenish","family":"Rahat","sequence":"first","affiliation":[{"name":"Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu-Xi","family":"Yu","sequence":"additional","affiliation":[{"name":"Pathology Core, National Heart Lung and Blood Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-3114","authenticated-orcid":true,"given":"Jacob","family":"Noeker","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apratim","family":"Mitra","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor M","family":"Kean","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-6502","authenticated-orcid":true,"given":"Russell H","family":"Knutsen","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular and Matrix Genetics, National Heart Lung and Blood Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-9744","authenticated-orcid":true,"given":"Danielle","family":"Springer","sequence":"additional","affiliation":[{"name":"Murine Phenotyping Core, National Heart Lung and Blood Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-1602","authenticated-orcid":true,"given":"Claudia 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