PUBLICATION

Mutants of the Zebrafish K+ Channel Hcn2b Exhibit Epileptic-like Behaviors

Authors
Rodríguez-Ortiz, R., Matínez-Torres, A.
ID
ZDB-PUB-211116-12
Date
2021
Source
International Journal of Molecular Sciences   22(21): (Journal)
Registered Authors
Martínez Torres, Ataúlfo, Rodríguez-Ortiz, Luis Roberto
Keywords
HCN channels, absence seizures, epilepsy, zebrafish
MeSH Terms
  • Animals
  • Behavior, Animal*
  • Epilepsy/etiology
  • Epilepsy/metabolism
  • Epilepsy/pathology*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism
  • Mutation*
  • Neurons/metabolism
  • Neurons/pathology*
  • Seizures/etiology
  • Seizures/metabolism
  • Seizures/pathology*
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
(all 16)
PubMed
34768904 Full text @ Int. J. Mol. Sci.
Abstract
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. Danio rerio has become a versatile organism to model a wide variety of diseases. In this work, we used CRISPR/Cas9 to generate hcn2b mutants in zebrafish, and characterized them molecularly and behaviorally. We obtained an hcn2b 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.
Genes / Markers
Marker Marker Type Name
hcn2bGENEhyperpolarization activated cyclic nucleotide-gated potassium channel 2b
1 - 1 of 1
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Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTaltered light dark cycleDays 7-13
hcn2buna101/una101controlAdult
hcn2buna101/una101standard conditionsPrim-5
hcn2buna101/una101standard conditionsPrim-25
hcn2buna101/una101standard conditionsLong-pec
hcn2buna101/una101standard conditionsLong-pec
hcn2buna101/una101standard conditionsLong-pec
hcn2buna101/una101standard conditionsLong-pec
hcn2buna101/una101standard conditionsProtruding-mouth
hcn2buna101/una101standard conditionsDays 7-13
1 - 10 of 18
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
una101
    		Small Deletion
    1 - 1 of 1
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    Human Disease / Model
    Human Disease Fish Conditions Evidence
    absence epilepsyTAS
    1 - 1 of 1
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    Sequence Targeting Reagents
    Target Reagent Reagent Type
    hcn2bCRISPR1-hcn2bCRISPR
    hcn2bCRISPR2-hcn2bCRISPR
    hcn2bCRISPR3-hcn2bCRISPR
    1 - 3 of 3
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    Fish
    Fish
    hcn2buna101/una101
    WT
    1 - 2 of 2
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    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    Citation
    Rodríguez-Ortiz, R., Matínez-Torres, A. (2021) Mutants of the Zebrafish K+ Channel Hcn2b Exhibit Epileptic-like Behaviors. International Journal of Molecular Sciences. 22(21):.