Mutants of the Zebrafish K+ Channel Hcn2b Exhibit Epileptic-like Behaviors
Por:
Rodriguez-Ortiz, Roberto, Matinez-Torres, Ataulfo
Publicada:
1 nov 2021
Resumen:
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.
Filiaciones:
Rodriguez-Ortiz, Roberto:
Cátedras CONACyT—Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus UNAM-Juriquilla, Universidad Nacional Autónoma de México, Querétaro, CP 76230, Mexico
Univ Nacl Autonoma Mexico, Catedras CONACyT, Dept Neurobiol Celular & Mol, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Mexico
Matinez-Torres, Ataulfo:
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus UNAM-Juriquilla, Universidad Nacional Autónoma de México, Querétaro, CP 76230, Mexico
Univ Nacl Autonoma Mexico, Dept Neurobiol Celular & Mol, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Mexico
gold, Gold
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