{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:54:22Z","timestamp":1787018062129,"version":"build-2736575974"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2008,1,15]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    <jats:italic>PRKAG2<\/jats:italic>\n                    mutations cause glycogen-storage cardiomyopathy, ventricular preexcitation, and conduction system degeneration. A genetic approach that utilizes a binary inducible transgenic system was used to investigate the disease mechanism and to assess preventability and reversibility of disease features in a mouse model of glycogen-storage cardiomyopathy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Transgenic (Tg) mice expressing a human N488I\n                    <jats:italic>PRKAG2<\/jats:italic>\n                    cDNA under control of the tetracycline-repressible \u03b1-myosin heavy chain promoter underwent echocardiography, ECG, and in vivo electrophysiology studies. Transgene suppression by tetracycline administration caused a reduction in cardiac glycogen content and was initiated either prenatally (Tg\n                    <jats:sup>OFF(E-8 weeks)<\/jats:sup>\n                    ) or at different time points during life (Tg\n                    <jats:sup>OFF(4\u201316 weeks)<\/jats:sup>\n                    , Tg\n                    <jats:sup>OFF(8\u201320 weeks)<\/jats:sup>\n                    , and Tg\n                    <jats:sup>OFF(&gt;20 weeks)<\/jats:sup>\n                    ). One group never received tetracycline, expressing transgene throughout life (Tg\n                    <jats:sup>ON<\/jats:sup>\n                    ). Tg\n                    <jats:sup>ON<\/jats:sup>\n                    mice developed cardiac hypertrophy followed by dilatation, ventricular preexcitation involving multiple accessory pathways, and conduction system disease, including sinus and atrioventricular node dysfunction.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Using an externally modifiable transgenic system, cardiomyopathy, cardiac dysfunction, and electrophysiological disorders were demonstrated to be reversible processes in\n                    <jats:italic>PRKAG2<\/jats:italic>\n                    disease. Transgene suppression during early postnatal development prevented the development of accessory electrical pathways but not cardiomyopathy or conduction system degeneration. Taken together, these data provide insight into mechanisms of cardiac\n                    <jats:italic>PRKAG2<\/jats:italic>\n                    disease and suggest that glycogen-storage cardiomyopathy can be modulated by lowering glycogen content in the heart.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.107.726752","type":"journal-article","created":{"date-parts":[[2007,12,24]],"date-time":"2007-12-24T20:34:44Z","timestamp":1198528484000},"page":"144-154","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["Reversibility of\n                    <i>PRKAG2<\/i>\n                    Glycogen-Storage Cardiomyopathy and Electrophysiological Manifestations"],"prefix":"10.1161","volume":"117","author":[{"given":"Cordula M.","family":"Wolf","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Arad","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferhaan","family":"Ahmad","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sanbe","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okan","family":"Toka","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Konno","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Morley","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Robbins","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles I.","family":"Berul","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Children\u2019s Hospital Boston (C.M.W., C.I.B.) and Department of Genetics (T.K., J.G.S., C.E.S.), Harvard Medical School, Boston, Mass; Sheba Medical Center (M.A.), Tel Aviv University, Israel; Cardiovascular Institute and Department of Medicine and Human Genetics (F.A.), University of Pittsburgh, Pittsburgh, Pa; Molecular Cardiovascular Biology (A.S., J.R.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio; Department of Cardiology, New York University..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214571"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.11.1215"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000258446.23525.37"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00044.2005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.05.020"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118154"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106143442403"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.04.062"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033349"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000075270.13497.2b"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00850-7"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.550806"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000065442.64694.9f"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7792603"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200214677"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.65"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119197"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.88.3.333"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(200001)217:1<75::AID-DVDY7>3.0.CO;2-L"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01973758"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00237-2"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00242-2"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.3.1073"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1940"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(78)90093-5"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(85)80095-4"},{"key":"e_1_3_2_27_2","first-page":"1389","volume":"75","year":"1982","unstructured":"Soria R, Guize L, Fernandez F, Chaouat JC, Chretien JM. 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