ZFIN ID: ZDB-PUB-191102-10
A zebrafish model of nondystrophic myotonia with sodium channelopathy
Nam, T.S., Zhang, J., Chandrasekaran, G., Jeong, I.Y., Li, W., Lee, S.H., Kang, K.W., Maeng, J.S., Kang, H., Shin, H.Y., Park, H.C., Kim, S., Choi, S.Y., Kim, M.K.
Date: 2019
Source: Neuroscience letters   714: 134579 (Journal)
Registered Authors: Choi, Seok-Yong, Jeong, Inyoung, Lee, So-Hyun, Li, Wenting, Park, Hae-Chul, Zhang, Jun
Keywords: Hyperkalemic periodic paralysis, Myotonia, Paramyotonia congenita, Sodium channel, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cold Temperature*
  • Disease Models, Animal*
  • Electromyography
  • Muscle, Skeletal/physiopathology*
  • Mutation, Missense
  • 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
  • Physical Exertion*
  • Zebrafish*
PubMed: 31669315 Full text @ Neurosci. Lett.
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:N440 K), and needle electromyography revealed increased number of myotonic discharges and positive sharp waves in the muscles of Tg(mylpfa:N440 K) 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:N440 K) 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.