Generation of a Triadin KnockOut Syndrome Zebrafish Model.

Different forms of sudden cardiac death have been described, including a recently identified form of genetic arrhythmogenic disorder, named "Triadin KnockOut Syndrome" (TKOS). TKOS is associated with recessive mutations in the gene, encoding for TRIADIN, but the pathogenic mechanism underlying the malignant phenotype has yet to be completely defined. Moreover, patients with TKOS are often refractory to conventional treatment, substantiating the need to identify new therapeutic strategies in order to prevent or treat cardiac events. The zebrafish () heart is highly comparable to the human heart in terms of functions, signal pathways and ion channels, representing a good model to study cardiac disorders. In this work, we generated the first zebrafish model for loss-of-function, by means of morpholino injections, and characterized its phenotype. Although we did not observe any gross cardiac morphological defect between loss-of-function embryos and controls, we found altered cardiac rhythm that was recovered by the administration of arrhythmic drugs. Our model will provide a suitable platform to study the effect of mutations and to perform drug screening to identify new pharmacological strategies for patients carrying TRDN mutations.