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

doi:10.3390/ijms22189720

Open AccessArticle

Generation of a Triadin KnockOut Syndrome Zebrafish Model

by

Vanilla Martina Vecchi

^1,†,

Marco Spreafico

^1,†

,

Alessia Brix

¹,

Anna Santoni

²,

Simone Sala

³

,

Anna Pistocchi

^1,*

,

Anna Marozzi

^1,† and

Chiara Di Resta

^2,†

¹

Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, LITA, Segrate, 20090 Milan, Italy

²

UOC Clinical Genomics, IRCCS San Raffaele Hospital, 20132 Milan, Italy

³

Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Hospital, 20132 Milan, Italy

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to the work.

Int. J. Mol. Sci. 2021, 22(18), 9720; https://doi.org/10.3390/ijms22189720

Submission received: 8 August 2021 / Revised: 31 August 2021 / Accepted: 3 September 2021 / Published: 8 September 2021

(This article belongs to the Section Molecular Genetics and Genomics)

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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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MDPI and ACS Style

Vecchi, V.M.; Spreafico, M.; Brix, A.; Santoni, A.; Sala, S.; Pistocchi, A.; Marozzi, A.; Di Resta, C. Generation of a Triadin KnockOut Syndrome Zebrafish Model. Int. J. Mol. Sci. 2021, 22, 9720. https://doi.org/10.3390/ijms22189720

AMA Style

Vecchi VM, Spreafico M, Brix A, Santoni A, Sala S, Pistocchi A, Marozzi A, Di Resta C. Generation of a Triadin KnockOut Syndrome Zebrafish Model. International Journal of Molecular Sciences. 2021; 22(18):9720. https://doi.org/10.3390/ijms22189720

Chicago/Turabian Style

Vecchi, Vanilla Martina, Marco Spreafico, Alessia Brix, Anna Santoni, Simone Sala, Anna Pistocchi, Anna Marozzi, and Chiara Di Resta. 2021. "Generation of a Triadin KnockOut Syndrome Zebrafish Model" International Journal of Molecular Sciences 22, no. 18: 9720. https://doi.org/10.3390/ijms22189720

APA Style

Vecchi, V. M., Spreafico, M., Brix, A., Santoni, A., Sala, S., Pistocchi, A., Marozzi, A., & Di Resta, C. (2021). Generation of a Triadin KnockOut Syndrome Zebrafish Model. International Journal of Molecular Sciences, 22(18), 9720. https://doi.org/10.3390/ijms22189720

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Generation of a Triadin KnockOut Syndrome Zebrafish Model

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