title: Retinal function and morphology in two zebrafish models of oculo-renal syndromes.
abstract: We characterized visual system defects in two recessive zebrafish mutants oval and elipsa. These mutants share the syndromic phenotype of outer retinal dystrophy in conjunction with cystic renal disorder. We tested the function of the larval visual system in a behavioural assay, eliciting optokinetic eye movements by high-contrast motion stimulation while recording eye movements in parallel. Visual stimulation did not elicit eye movements in mutant larvae, while spontaneous eye movements could be observed. The retina proved to be unresponsive to light using electroretinography, indicative of a defect in the outer retina. Histological analysis of mutant retinas revealed progressive degeneration of photoreceptors, initiated in central retinal locations and spreading to more peripheral regions with increasing age. The inner retina remains unaffected by the mutation. Photoreceptors display cell type-specific immunoreactivity prior to apoptotic cell death, arguing for a dystrophic defect. Genomic mapping employing simple sequence-length polymorphisms located both mutations on different regions of zebrafish linkage group 9. These mutants may serve as accessible animal models of human outer retinal dystrophies, including oculo-renal diseases, and show the general usefulness of a behavioural genetic approach to study visual system development in the model vertebrate zebrafish.
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D016923:Cell Death; D002454:Cell Differentiation; D002874:Chromosome Mapping / Q000379:methods; D004195:Disease Models, Animal; D004596:Electroretinography / Q000379:methods; D005133:Eye Movements; D005808:Genes, Recessive; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007814:Larva; D008027:Light; D009154:Mutation; D017120:Nystagmus, Optokinetic / Q000502:physiology; D010775:Photic Stimulation; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D013194:Staining and Labeling; D015027:Zebrafish