Transgenic animal model for catecholaminergic polymorphic ventricular tachycardia (CPVT) and use thereof
OwnerSilvia G. Priori, Carlo Napolitanoinventors
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Abstract
The present invention refers to non-human transgenic mammals, preferably rodents, or mice, which comprise a mutation in the gene encoding for the cardiac ryanodine receptor (RyR2). Transgenic animals carrying the amino acid change R4496C in the RyR2 protein show a phenotype similar to that of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) (OMIM: 604772). Further provided are methods for using these animals as in vivo model of Catecholaminergic Polymorphic Ventricular Tachycardia and RyR2 dependent arrhythmias, in drug screening and for understanding the molecular basis of RyR2 dependent arrhythmias.
Claims20
A transgenic mouse model for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) on a genetic basis carrying an R4496C mutation in the cardiac Ryanodine receptor (RyR2) gene in a heterozygous form, wherein sustained ectopic activity leading to bidirectional Ventricular Tachycardia (VT) and Ventricular Fibrillation (VF) is obtained by exposure of the mouse to a RyR-agonist (caffeine) or during adrenergic stimulation and wherein said transgenic mouse model further exhibits the following characteristics:
- adrenergically mediated arrhythmogenesis;
- normal electrocardiogram at baseline;
- lack of fatty fibrous infiltration in the heart;
- absence of extra-cardiac abnormalities;
- incomplete response to beta blocker therapy;
- and
- incomplete penetrance.
Dependencies are inferred from the claim text.