{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:58:11Z","timestamp":1790611091282,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,7,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The epithelial growth factor receptor family of tyrosine kinases modulates embryonic formation of semilunar valves. We hypothesized that mice heterozygous for a dominant loss\u2010of\u2010function mutation in epithelial growth factor receptor, which are\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              mice, would develop anomalous aortic valves, valve dysfunction, and valvular cardiomyopathy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Aortic valves from\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              mice and control mice were examined by light microscopy at 2.5 to 4\u00a0months of age. Additional\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              and control mice underwent echocardiography at 2.5, 4.5, 8, and 12\u00a0months of age, followed by histologic examination. In young mice, microscopy revealed anatomic anomalies in 79% of\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              aortic valves, which resembled human unicuspid aortic valves. Anomalies were not observed in control mice. At 12\u00a0months of age, histologic architecture was grossly distorted in\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              aortic valves. Echocardiography detected moderate or severe aortic regurgitation, or aortic stenosis was present in 38% of\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              mice at 2.5\u00a0months of age (N=24) and in 74% by 8\u00a0months of age. Left ventricular enlargement, hypertrophy, and reversion to a fetal myocardial gene expression program occurred in\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              mice with aortic valve dysfunction, but not in\n              <jats:italic>Egfr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Vel\/+<\/jats:italic>\n              <\/jats:sup>\n              mice with near\u2010normal aortic valve function. Myocardial fibrosis was minimal or absent in all groups.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">A new mouse model uniquely recapitulates salient functional, structural, and histologic features of human unicuspid aortic valve disease, which are phenotypically distinct from other forms of congenital aortic valve disease. The new model may be useful for elucidating mechanisms by which congenitally anomalous aortic valves become critically dysfunctional.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.006908","type":"journal-article","created":{"date-parts":[[2018,6,30]],"date-time":"2018-06-30T09:15:10Z","timestamp":1530350110000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Discovery of an Experimental Model of Unicuspid Aortic Valve"],"prefix":"10.1161","volume":"7","author":[{"given":"Robert M.","family":"Weiss","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"Lund","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy A.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa K.","family":"Kafa","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phanicharan","family":"Sistla","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardik","family":"Doshi","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Q.","family":"Shao","sequence":"additional","affiliation":[{"name":"The Central Microscopy Core Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi N.","family":"El Accaoui","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Otto","sequence":"additional","affiliation":[{"name":"Division of Cardiology University of Washington School of Medicine Seattle WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"Heistad","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Carver College of Medicine University of Iowa Iowa City IA"},{"name":"Department of Pharmacology Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.183216"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.08.074"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.543280"},{"key":"e_1_3_2_5_2","first-page":"79","article-title":"Unicuspid aortic valve in adults: a systematic review","volume":"19","author":"Mookadam F","year":"2010","unstructured":"Mookadam F, Thota VR, Garcia\u2010Lopez AM, Emani UR, Alharthi MS, Zamorano J, Khandheria BK. 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