PUBLICATION

Generation of a Triadin KnockOut Syndrome Zebrafish Model

Authors
Vecchi, V.M., Spreafico, M., Brix, A., Santoni, A., Sala, S., Pistocchi, A., Marozzi, A., Di Resta, C.
ID
ZDB-PUB-210929-14
Date
2021
Source
International Journal of Molecular Sciences   22(18): (Journal)
Registered Authors
Keywords
Triadin KnockOut Syndrome, arrhythmic drugs, heart defects, zebrafish
MeSH Terms
  • Animals
  • Arrhythmias, Cardiac/diagnosis
  • Arrhythmias, Cardiac/genetics
  • Carrier Proteins
  • Death, Sudden, Cardiac/etiology*
  • Disease Models, Animal*
  • Gene Expression
  • Gene Knockout Techniques
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Loss of Function Mutation
  • Muscle Fibers, Skeletal/metabolism
  • Muscle Fibers, Skeletal/pathology
  • Muscle Proteins/deficiency*
  • Phenotype
  • Syndrome
  • Zebrafish
PubMed
34575879 Full text @ Int. J. Mol. Sci.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping