A zebrafish model of nondystrophic myotonia with sodium channelopathy

•Nondystrophic myotonias are disorders of Na+ and Cl− channels in skeletal muscles.•We generated transgenic zebrafish expressing a human mutant allele of Na+ channels.•The transgenic zebrafish showed electromyographic features of transgenic zebrafish.•The zebrafish displayed swimming behavior sugges...

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Bibliographic Details
Published in:Neuroscience letters 2020-01, Vol.714, p.134579-134579, Article 134579
Main Authors: Nam, Tai-Seung, Zhang, Jun, Chandrasekaran, Gopalakrishnan, Jeong, In Young, Li, Wenting, Lee, So-Hyun, Kang, Kyung-Wook, Maeng, Jin-Soo, Kang, Hyuno, Shin, Hee-Young, Park, Hae-Chul, Kim, Sohee, Choi, Seok-Yong, Kim, Myeong-Kyu
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Cold Temperature
Disease Models, Animal
Electromyography
Hyperkalemic periodic paralysis
Muscle, Skeletal - physiopathology
Mutation, Missense
Myotonia
Myotonia - genetics
Myotonia - physiopathology
Myotonia Congenita - genetics
Myotonia Congenita - physiopathology
Myotonic Disorders - genetics
Myotonic Disorders - physiopathology
NAV1.4 Voltage-Gated Sodium Channel - genetics
Paralysis, Hyperkalemic Periodic - genetics
Paralysis, Hyperkalemic Periodic - physiopathology
Paramyotonia congenita
Physical Exertion
Sodium channel
Zebrafish
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Summary:•Nondystrophic myotonias are disorders of Na+ and Cl− channels in skeletal muscles.•We generated transgenic zebrafish expressing a human mutant allele of Na+ channels.•The transgenic zebrafish showed electromyographic features of transgenic zebrafish.•The zebrafish displayed swimming behavior suggestive of nondystrophic myotonias.•This zebrafish model is a good vertebrate model of human nondystrophic myotonias. Nondystrophic myotonias are disorders of Na+ (Nav1.4 or SCN4A) and Cl− (CLCN1) channels in skeletal muscles, and frequently show phenotype heterogeneity. The molecular mechanism underlying their pathophysiology and phenotype heterogeneity remains unclear. As zebrafish models have been recently exploited for studies of the pathophysiology and phenotype heterogeneity of various human genetic diseases, a zebrafish model may be useful for delineating nondystrophic myotonias. Here, we generated transgenic zebrafish expressing a human mutant allele of SCN4A, referred to as Tg(mylpfa:N440K), and needle electromyography revealed increased number of myotonic discharges and positive sharp waves in the muscles of Tg(mylpfa:N440K) than in controls. In addition, forced exercise test at a water temperature of 24 °C showed a decrease in the distance moved, time spent in and number of visits to the zone with stronger swimming resistance. Finally, a forced exercise test at a water temperature of 18 °C exhibited a higher number of dive-bombing periods and drifting-down behavior than in controls. These findings indicate that Tg(mylpfa:N440K) is a good vertebrate model of exercise- and cold-induced human nondystrophic myotonias. This zebrafish model may contribute to provide insight into the pathophysiology of myotonia in sodium channelopathy and could be used to explore a new therapeutic avenue.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2019.134579