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Generation of a Triadin KnockOut Syndrome Zebrafish Model
Authors:Vanilla Martina Vecchi  Marco Spreafico  Alessia Brix  Anna Santoni  Simone Sala  Anna Pistocchi  Anna Marozzi  Chiara Di Resta
Affiliation:1.Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, LITA, Segrate, 20090 Milan, Italy; (V.M.V.); (M.S.); (A.B.); (A.M.);2.UOC Clinical Genomics, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (A.S.); (C.D.R.);3.Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Hospital, 20132 Milan, Italy;
Abstract: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 TRDN 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 (Danio rerio) 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 trdn loss-of-function, by means of trdn morpholino injections, and characterized its phenotype. Although we did not observe any gross cardiac morphological defect between trdn 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 TRDN mutations and to perform drug screening to identify new pharmacological strategies for patients carrying TRDN mutations.
Keywords:Triadin KnockOut Syndrome  heart defects  zebrafish  arrhythmic drugs
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