Generation of a Triadin KnockOut Syndrome Zebrafish Model.
Vanilla Martina VecchiMarco SpreaficoAlessia BrixAnna SantoniSimone SalaAnna PistocchiAnna MarozziChiara Di RestaPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- left ventricular
- heart failure
- end stage renal disease
- endothelial cells
- newly diagnosed
- genome wide
- ejection fraction
- emergency department
- blood pressure
- copy number
- gene expression
- high throughput
- prognostic factors
- single cell
- intellectual disability
- induced pluripotent stem cells
- platelet rich plasma
- genome wide identification