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.