{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:13:05Z","timestamp":1791328385189,"version":"4.3.1"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,10,26]]},"abstract":"<jats:p>\n            The cardiac sarco(endo)plasmic reticulum Ca\n            <jats:sup>2+<\/jats:sup>\n            -ATPase gene (\n            <jats:italic>ATP2A2<\/jats:italic>\n            ) encodes the following two different protein isoforms: SERCA2a (muscle-specific) and SERCA2b (ubiquitous). We have investigated whether this isoform specificity is required for normal cardiac function. Gene targeting in mice successfully disrupted the splicing mechanism responsible for generating the SERCA2a isoform. Homozygous\n            <jats:italic>SERCA2a<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice displayed a complete loss of SERCA2a mRNA and protein resulting in a switch to the SERCA2b isoform. The expression of SERCA2b mRNA and protein in hearts of\n            <jats:italic>SERCA2a<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice corresponded to only 50% of wild-type SERCA2 levels. Cardiac phospholamban mRNA levels were unaltered in\n            <jats:italic>SERCA2a<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, but total phospholamban protein levels increased 2-fold. The transgenic phenotype was characterized by a \u224820% increase in embryonic and neonatal mortality (early phenotype), with histopathologic evidence of major cardiac malformations. Adult\n            <jats:italic>SERCA2a<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            animals (adult phenotype) showed a reduced spontaneous nocturnal activity and developed a mild compensatory concentric cardiac hypertrophy with impaired cardiac contractility and relaxation, but preserved \u03b2-adrenergic response. Ca\n            <jats:sup>2+<\/jats:sup>\n            uptake levels in\n            <jats:italic>SERCA2a<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            cardiac homogenates were reduced by \u224850%. In isolated cells, relaxation and Ca\n            <jats:sup>2+<\/jats:sup>\n            removal by the SR were significantly reduced. Comparison of our data with those obtained in mice expressing similar cardiac levels of SERCA2a instead of SERCA2b indicate the importance of the muscle-specific SERCA2a isoform for normal cardiac development and for the cardiac contraction-relaxation cycle.\n          <\/jats:p>","DOI":"10.1161\/hh2101.098466","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:32:49Z","timestamp":1191004369000},"page":"838-846","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":87,"title":["Replacement of the Muscle-Specific Sarcoplasmic Reticulum Ca\n            <sup>2+<\/sup>\n            -ATPase Isoform SERCA2a by the Nonmuscle SERCA2b Homologue Causes Mild Concentric Hypertrophy and Impairs Contraction-Relaxation of the Heart"],"prefix":"10.1161","volume":"89","author":[{"given":"Mark","family":"Ver Heyen","sequence":"first","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Heymans","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Antoons","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Reed","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthu","family":"Periasamy","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonaventure","family":"Awede","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Lebacq","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vangheluwe","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke","family":"Dewerchin","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desire\u0301","family":"Collen","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Sipido","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Carmeliet","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Wuytack","sequence":"additional","affiliation":[{"name":"From the Laboratories of Physiology (M.V.H., P.V., F.W.) and Cardiology (G.A., K.S.) and the Center for Transgene Technology and Gene Therapy (S.H., M.D., D.C., P.C.), Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Belgium; GenomatixUSA (T.R.), Cincinnati, Ohio; Department of Physiology and Cell Biology (M.P.), Ohio State University College of Medicine and Health Sciences, Columbus, Ohio; and De\u0301partement de Physiologie (B.A., J.L.), Universite\u0301 Catholique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.3.C775"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83540-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50426-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3030979"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.76.4.616"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00120-0"},{"key":"e_1_3_3_7_2","first-page":"125","volume":"157","year":"1996","unstructured":"Dillmann WH. 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