Recessive mutations in KCNJ10, which encodes an inwardly rectifying potassium 
channel, were recently identified as the cause of EAST syndrome, a severe and 
disabling multi-organ disorder consisting of epilepsy, ataxia, sensorineural 
deafness and tubulopathy that becomes clinically apparent with seizures in 
infancy. A Kcnj10 knockout mouse shows postnatal mortality and is therefore not 
suitable for drug discovery. Because zebrafish are ideal for in vivo screening 
for potential therapeutics, we tested whether kcnj10 knockdown in zebrafish 
would fill this need. We cloned zebrafish kcnj10 and demonstrated that its 
function is equivalent to that of human KCNJ10. We next injected splice- and 
translation-blocking kcnj10 antisense morpholino oligonucleotides and reproduced 
the cardinal symptoms of EAST syndrome - ataxia, epilepsy and renal tubular 
defects. Several of these phenotypes could be assayed in an automated manner. We 
could rescue the morphant phenotype with complementary RNA (cRNA) encoding human 
wild-type KCNJ10, but not with cRNA encoding a KCNJ10 mutation identified in 
individuals with EAST syndrome. Our results suggest that zebrafish will be a 
valuable tool to screen for compounds that are potentially therapeutic for EAST 
syndrome or its individual symptoms. Knockdown of kcnj10 represents the first 
zebrafish model of a salt-losing tubulopathy, which has relevance for blood 
pressure control.