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 TRDN gene, encoding for TRIADIN, but the pathogenic mechanism underlying...

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Published inInternational journal of molecular sciences Vol. 22; no. 18; p. 9720
Main Authors Vecchi, Vanilla Martina, Spreafico, Marco, Brix, Alessia, Santoni, Anna, Sala, Simone, Pistocchi, Anna, Marozzi, Anna, Di Resta, Chiara
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 08.09.2021
MDPI
Subjects
arrhythmic drugs
Asymptomatic
Cardiac arrhythmia
Danio rerio
Drug dosages
Drug screening
Edema
Embryos
Genotype & phenotype
Heart
heart defects
Ion channels
Kinases
Morphology
Musculoskeletal system
Mutation
Patients
Pediatrics
Phenotypes
Proteins
Triadin KnockOut Syndrome
Zebrafish
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Summary: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.
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These authors contributed equally to the work.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22189720