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http://purl.uniprot.org/citations/22298808http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22298808http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

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.

Objective

We intended to evaluate whether viral gene transfer of wild-type CASQ2 may rescue the broad spectrum of abnormalities caused by mutant CASQ2.

Methods and results

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.

Conclusions

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."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.111.263939"xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Auricchio A."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Napolitano C."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Priori S.G."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Boncompagni S."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Volpe P."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Protasi F."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Denegri M."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Villani L."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"Avelino-Cruz J.E."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/author"De Simone S.A."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/pages"663-668"xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/title"Viral gene transfer rescues arrhythmogenic phenotype and ultrastructural abnormalities in adult calsequestrin-null mice with inherited arrhythmias."xsd:string
http://purl.uniprot.org/citations/22298808http://purl.uniprot.org/core/volume"110"xsd:string
http://purl.uniprot.org/citations/22298808http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22298808
http://purl.uniprot.org/citations/22298808http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22298808
http://purl.uniprot.org/uniprot/#_E9Q9K5-mappedCitation-22298808http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22298808
http://purl.uniprot.org/uniprot/#_A0A1Y7VJP1-mappedCitation-22298808http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22298808
http://purl.uniprot.org/uniprot/#_A0A1Y7VK09-mappedCitation-22298808http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22298808
http://purl.uniprot.org/uniprot/#_A0A1W2P6F3-mappedCitation-22298808http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22298808
http://purl.uniprot.org/uniprot/#_A0A1W2P8G7-mappedCitation-22298808http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22298808
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