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Project

The elucidation of pathogenesis and modes of inheritance of catecholaminergic polymorphic ventricular tachycardia using cardiac optical imaging in zebrafish.

Sudden death in the young is primarily caused by inherited diseases of the heart. These conditions are frequently caused by mutations in genes responsible for maintaining a regular heartbeat. One of these cardiac disorders is catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by abnormal calcium signaling in the heart. Both in the literature and in our own cardiogenetics clinic, several CPVT families with an uncertain inheritance pattern have been discovered. In order to investigate the effect of a presumed splice site mutation identified in the CASQ2 gene of a CPVT patient in our cardiogenetics clinic, I will perform a Minigene-assay. I have developed a zebrafish line in which cardiac electrical and chemical calcium signals are converted into fluorescent light signals, allowing in vivo imaging of cardiac action potentials and calcium transients. Using CRISPR/Cas9, I developed a casq2 knock-out zebrafish model for CPVT. By overexpressing mutant CASQ2 mRNA in these zebrafish, either alone or in combination with wildtype mRNA, I will be able to model human homozygous and heterozygous states. This will not only improve further diagnostic testing in CPVT but also ameliorate risk stratification and refine personalized management.
Date:1 Apr 2021 →  31 Mar 2022
Keywords:ZEBRAFISH, LIGHT SHEET MICROSCOPY, CARDIAC ARRHYTHMIA, GENETICS
Disciplines:Cardiology, Genetics