Investigations of photoreceptor synaptic transmission and light adaptationin the zebrafish visual mutant nrc

PURPOSE. TO characterize the retinal physiology of the zebrafish visual mut ant no optokinetic response c (nrc) and to identify the genetic map positio n of the nrc mutation. METHODS. Electroretinograms were recorded from wild-type and nrc zebrafish larvae between 5 to 6 days postfertilization. Responses to flash stimuli, O n and Off responses to prolonged light stimuli, and responses to flash stim uli with constant background illumination were characterized. The glutamate agonist, 2-amino-4-phosphonobutyric acid (APB) was used to examine the pho toreceptor specific a-wave component of the electroretinogram. Amplified fr agment length polymorphism methodology was used to place the nrc mutation o n the zebrafish genomic map. RESULTS. nrc and wild-type zebrafish larvae 5 to G days postfertilization h ave similar threshold responses to light, but the b-wave of the nrc electro retinogram is significantly delayed and reduced in amplitude. On and Off re sponses of nrc larvae to prolonged light have multiple oscillations that do not occur in normal zebrafish larvae after 5 days postfertilization. Analy sis of the b-wave demonstrated a light adaptation defect in nrc that causes saturation at background light levels approximately 1 order of magnitude l ess than those with wild-type larvae. Application of the glutamate analog, APE, uncovered the photoreceptor component of the electroretinogram and rev ealed a light adaptation defect in nrc photoreceptors. The nrc mutation was placed approximately 0.2 cM from sequence length polymorphism marker Z7504 on linkage group 10. CONCLUSIONS. The zebrafish mutant nrc is a possible model for human retinal disease. nrc has defects in photoreceptor synaptic transmission and light adaptation. The nrc mutant phenotype shows striking similarities with pheno types of dystrophin glycoprotein complex mutants, including patients with D uchenne/Becker muscular dystrophy. Localization of the nrc mutation now mak es it possible to evaluate candidate genes and clone the nrc gene.