{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:23:42Z","timestamp":1792797822496,"version":"4.5.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,6,5]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    \u2014Transforming growth factor-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    (TGF-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    ) is a member of a family of growth factors with the potential to modify multiple processes. Mice deficient in the TGF-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    gene die around birth and show a variety of defects of different organs, including the heart.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods and Results<\/jats:italic>\n                    \u2014We studied the hearts of TGF-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    \u2013null mouse embryos from 11.5 to 18.5 days of gestation to analyze the types of defects and determine which processes of cardiac morphogenesis are affected by the absence of TGF-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    . Analysis of serial sections revealed malformations of the outflow tract (typically a double-outlet right ventricle) in 87.5%. There was 1 case of common arterial trunk. Abnormal thickening of the semilunar valves was seen in 4.2%. Associated malformations of the atrioventricular (AV) canal were found in 62.5% and were composed of perimembranous inlet ventricular septal defects (37.5%), AV valve thickening (33.3%), overriding tricuspid valve (25.0%), and complete AV septal defects (4.2%). Anomalies of the aorta and its branches were seen in 33.3%. Immunohistochemical staining showed failure of myocardialization of the mesenchyme of the atrial septum and the ventricular outflow tract as well as deficient valve differentiation. Morphometry documented this to be associated with absence of the normal decrease of total endocardial cushion volume in the older stages. Apoptosis in TGF-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    \u2013knockout mice was increased, although regional distribution was normal.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    \u2014TGF-\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    \u2013knockout mice exhibited characteristic cardiovascular anomalies comparable to malformations seen in the human population.\n                  <\/jats:p>","DOI":"10.1161\/01.cir.103.22.2745","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:09:32Z","timestamp":1339445372000},"page":"2745-2752","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":269,"title":["Double-Outlet Right Ventricle and Overriding Tricuspid Valve Reflect Disturbances of Looping, Myocardialization, Endocardial Cushion Differentiation, and Apoptosis in TGF-\u03b2\n                    <sub>2<\/sub>\n                    \u2013Knockout Mice"],"prefix":"10.1161","volume":"103","author":[{"given":"Ulrike","family":"Bartram","sequence":"first","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danie\u0308l G. M.","family":"Molin","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambertus J.","family":"Wisse","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azhar","family":"Mohamad","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Philip","family":"Sanford","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Doetschman","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Speer","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Poelmann","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana C.","family":"Gittenberger-de Groot","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Embryology, Leiden University, Leiden, the Netherlands (D.G.M.M., L.J.W., R.E.P., A.C.G.-d.G.); the University Children\u2019s Hospital Wu\u0308rzburg, Wu\u0308rzburg, Germany (U.B., C.P.S.); and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio (A.M., L.P.S., T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.06.110190.003121"},{"key":"e_1_3_2_2_2","first-page":"323","volume":"3","year":"1988","unstructured":"Barton DE, Foellmer BE, Du J, et al. 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