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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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Autores principales: Vecchi, Vanilla Martina, Spreafico, Marco, Brix, Alessia, Santoni, Anna, Sala, Simone, Pistocchi, Anna, Marozzi, Anna, Di Resta, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471218/
https://www.ncbi.nlm.nih.gov/pubmed/34575879
http://dx.doi.org/10.3390/ijms22189720
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author Vecchi, Vanilla Martina
Spreafico, Marco
Brix, Alessia
Santoni, Anna
Sala, Simone
Pistocchi, Anna
Marozzi, Anna
Di Resta, Chiara
author_facet Vecchi, Vanilla Martina
Spreafico, Marco
Brix, Alessia
Santoni, Anna
Sala, Simone
Pistocchi, Anna
Marozzi, Anna
Di Resta, Chiara
author_sort Vecchi, Vanilla Martina
collection PubMed
description 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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spelling pubmed-84712182021-09-27 Generation of a Triadin KnockOut Syndrome Zebrafish Model Vecchi, Vanilla Martina Spreafico, Marco Brix, Alessia Santoni, Anna Sala, Simone Pistocchi, Anna Marozzi, Anna Di Resta, Chiara Int J Mol Sci Article 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. MDPI 2021-09-08 /pmc/articles/PMC8471218/ /pubmed/34575879 http://dx.doi.org/10.3390/ijms22189720 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vecchi, Vanilla Martina
Spreafico, Marco
Brix, Alessia
Santoni, Anna
Sala, Simone
Pistocchi, Anna
Marozzi, Anna
Di Resta, Chiara
Generation of a Triadin KnockOut Syndrome Zebrafish Model
title Generation of a Triadin KnockOut Syndrome Zebrafish Model
title_full Generation of a Triadin KnockOut Syndrome Zebrafish Model
title_fullStr Generation of a Triadin KnockOut Syndrome Zebrafish Model
title_full_unstemmed Generation of a Triadin KnockOut Syndrome Zebrafish Model
title_short Generation of a Triadin KnockOut Syndrome Zebrafish Model
title_sort generation of a triadin knockout syndrome zebrafish model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471218/
https://www.ncbi.nlm.nih.gov/pubmed/34575879
http://dx.doi.org/10.3390/ijms22189720
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