Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors

Epilepsy is a chronic neurological disorder that affects 50 million people worldwide. The most common form of epilepsy is idiopathic, where most of the genetic defects of this type of epilepsy occur in ion channels. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by...

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Auteurs principaux:	Roberto Rodríguez-Ortiz, Ataúlfo Matínez-Torres
Format:	article
Langue:	EN
Publié:	MDPI AG 2021
Sujets:	HCN channels epilepsy absence seizures zebrafish Biology (General) QH301-705.5 Chemistry QD1-999
Accès en ligne:	https://doaj.org/article/18e6c5677bdc465a8e7b7b32c1d6e054
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spelling	oai:doaj.org-article:18e6c5677bdc465a8e7b7b32c1d6e0542021-11-11T16:56:21ZMutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors10.3390/ijms2221114711422-00671661-6596https://doaj.org/article/18e6c5677bdc465a8e7b7b32c1d6e0542021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11471https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Epilepsy is a chronic neurological disorder that affects 50 million people worldwide. The most common form of epilepsy is idiopathic, where most of the genetic defects of this type of epilepsy occur in ion channels. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization, and are mainly expressed in the heart and central and peripheral nervous systems. In humans, four HCN genes have been described, and emergent clinical data shows that dysfunctional HCN channels are involved in epilepsy. <i>Danio rerio</i> has become a versatile organism to model a wide variety of diseases. In this work, we used CRISPR/Cas9 to generate <i>hcn2b</i> mutants in zebrafish, and characterized them molecularly and behaviorally. We obtained an <i>hcn2b</i> mutant allele with an 89 bp deletion that produced a premature stop codon. The mutant exhibited a high mortality rate in its life span, probably due to its sudden death. We did not detect heart malformations or important heart rate alterations. Absence seizures and moderate seizures were observed in response to light. These seizures rarely caused instant death. The results show that mutations in the Hcn2b channel are involved in epilepsy and provide evidence of the advantages of zebrafish to further our understanding of the pathogenesis of epilepsy.Roberto Rodríguez-OrtizAtaúlfo Matínez-TorresMDPI AGarticleHCN channelsepilepsyabsence seizureszebrafishBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11471, p 11471 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HCN channels epilepsy absence seizures zebrafish Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	HCN channels epilepsy absence seizures zebrafish Biology (General) QH301-705.5 Chemistry QD1-999 Roberto Rodríguez-Ortiz Ataúlfo Matínez-Torres Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors
description	Epilepsy is a chronic neurological disorder that affects 50 million people worldwide. The most common form of epilepsy is idiopathic, where most of the genetic defects of this type of epilepsy occur in ion channels. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarization, and are mainly expressed in the heart and central and peripheral nervous systems. In humans, four HCN genes have been described, and emergent clinical data shows that dysfunctional HCN channels are involved in epilepsy. <i>Danio rerio</i> has become a versatile organism to model a wide variety of diseases. In this work, we used CRISPR/Cas9 to generate <i>hcn2b</i> mutants in zebrafish, and characterized them molecularly and behaviorally. We obtained an <i>hcn2b</i> mutant allele with an 89 bp deletion that produced a premature stop codon. The mutant exhibited a high mortality rate in its life span, probably due to its sudden death. We did not detect heart malformations or important heart rate alterations. Absence seizures and moderate seizures were observed in response to light. These seizures rarely caused instant death. The results show that mutations in the Hcn2b channel are involved in epilepsy and provide evidence of the advantages of zebrafish to further our understanding of the pathogenesis of epilepsy.
format	article
author	Roberto Rodríguez-Ortiz Ataúlfo Matínez-Torres
author_facet	Roberto Rodríguez-Ortiz Ataúlfo Matínez-Torres
author_sort	Roberto Rodríguez-Ortiz
title	Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors
title_short	Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors
title_full	Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors
title_fullStr	Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors
title_full_unstemmed	Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors
title_sort	mutants of the zebrafish k<sup>+</sup> channel hcn2b exhibit epileptic-like behaviors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/18e6c5677bdc465a8e7b7b32c1d6e054
work_keys_str_mv	AT robertorodriguezortiz mutantsofthezebrafishksupsupchannelhcn2bexhibitepilepticlikebehaviors AT ataulfomatineztorres mutantsofthezebrafishksupsupchannelhcn2bexhibitepilepticlikebehaviors
_version_	1718432162816983040

Mutants of the Zebrafish K<sup>+</sup> Channel Hcn2b Exhibit Epileptic-like Behaviors

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