{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:44:27Z","timestamp":1791074667594,"version":"4.1.0"},"reference-count":11,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,3,2]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Catecholaminergic polymorphic ventricular tachycardia is an inherited disease that predisposes to cardiac arrest and sudden death. The disease is associated with mutations in the genes encoding for the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2). CASQ2 mutations lead to a major loss of CASQ2 monomers, possibly because of enhanced degradation of the mutant protein. The decrease of CASQ2 is associated with a reduction in the levels of Triadin (TrD) and Junctin (JnC), two proteins that form, with CASQ2 and RyR2, a macromolecular complex devoted to control of calcium release from the sarcoplasmic reticulum.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We intended to evaluate whether viral gene transfer of wild-type CASQ2 may rescue the broad spectrum of abnormalities caused by mutant CASQ2.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We used an adeno-associated serotype 9 viral vector to express a green fluorescent protein-tagged CASQ2 construct. Twenty weeks after intraperitoneal injection of the vector in neonate CASQ2 KO mice, we observed normalization of the levels of calsequestrin, triadin, and junctin, rescue of electrophysiological and ultrastructural abnormalities caused by CASQ2 ablation, and lack of life-threatening arrhythmias.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We have proven the concept that induction of CASQ2 expression in knockout mice reverts the molecular, structural, and electric abnormalities and prevents life-threatening arrhythmias in CASQ2-defective catecholaminergic polymorphic ventricular tachycardia mice. These data support the view that development of CASQ2 viral gene transfer could have clinical application.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.111.263939","type":"journal-article","created":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T06:14:23Z","timestamp":1328076863000},"page":"663-668","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":84,"title":["Viral Gene Transfer Rescues Arrhythmogenic Phenotype and Ultrastructural Abnormalities in Adult Calsequestrin-Null Mice With Inherited Arrhythmias"],"prefix":"10.1161","volume":"110","author":[{"given":"Marco","family":"Denegri","sequence":"first","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Everardo","family":"Avelino-Cruz","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Boncompagni","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano Andrea","family":"De Simone","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Auricchio","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Villani","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pompeo","family":"Volpe","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feliciano","family":"Protasi","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Napolitano","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Giuliana","family":"Priori","sequence":"additional","affiliation":[{"name":"From the Molecular Cardiology (M.D., J.E., S.A.D.S., C.N., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Cardiovascular Genetics Program (C.N., S.G.P.), The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY; Department of Molecular Medicine (S.G.P.), University of Pavia, Pavia, Italy; CeSI-Center for Research on Ageing &amp; DNI-Department of Neuroscience and Imaging (S.B., F.P.), University G. d'Annunzio, Chieti, Italy; Telethon Institute of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.226845"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000020013.73106.D8"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.2.196"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/324565"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31080"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.171660"},{"key":"e_1_3_5_8_2","first-page":"2510","article-title":"Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia","volume":"116","author":"Knollmann BC","year":"2006","unstructured":"Knollmann BC, Chopra N, Hlaing T, Akin B, Yang T, Ettensohn K, Knollmann BE, Horton KD, Weissman NJ, Holinstat I, Zhang W, Roden DM, Jones LR, Franzini-Armstrong C, Pfeifer K. Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia. J Clin Invest. 2006;116:2510\u20132520.","journal-title":"J Clin Invest"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1139\/H09-017"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1942"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.111.247338"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.022889"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.111.263939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:30:52Z","timestamp":1715571052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.111.263939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,2]]},"references-count":11,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,3,2]]}},"alternative-id":["10.1161\/CIRCRESAHA.111.263939"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.111.263939","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,2]]},"assertion":[{"value":"2011-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-01-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-01-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}