ZFIN ID: ZDB-PUB-991109-28
Genetic disorders of vision revealed by a behavioral screen of 400 essential loci in zebrafish
Neuhauss, S.C.F., Biehlmaier, O., Seeliger, M.W., Das, T., Kohler, K., Harris, W.A., and Baier, H.
Date: 1999
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   19(19): 8603-8615 (Journal)
Registered Authors: Baier, Herwig, Biehlmaier, Oliver, Harris, William A., Neuhauss, Stephan
Keywords: visual system; vision; retina; tectum; optomotor; optokinetic; albinism; photoreceptor; retinal ganglion cell; outer-retina dystrophy; retinitis pigmentosa; retinal degeneration; mutant screen; mutation; zebrafish; Danio rerio; forward genetics; ERG
MeSH Terms:
  • Albinism/genetics
  • Albinism/veterinary
  • Alleles
  • Animals
  • Axons/physiology
  • Blindness/genetics
  • Blindness/veterinary
  • Fish Diseases/genetics*
  • Fish Diseases/physiopathology
  • Lens, Crystalline/pathology
  • Lens, Crystalline/physiopathology
  • Melanins/deficiency
  • Mutation*
  • Nystagmus, Optokinetic
  • Vision Disorders/genetics
  • Vision Disorders/physiopathology
  • Vision Disorders/veterinary*
  • Visual Pathways/pathology
  • Visual Pathways/physiopathology*
  • Zebrafish/genetics*
PubMed: 10493760
We examined optokinetic and optomotor responses of 450 zebrafish mutants, which were isolated previously based on defects in organ formation, tissue patterning, pigmentation, axon guidance, or other visible phenotypes. These strains carry single point mutations in >400 essential loci. We asked which fraction of the mutants develop blindness or other types of impairments specific to the visual system. Twelve mutants failed to respond in either one or both of our assays. Subsequent histological and electroretinographic analysis revealed unique deficits at various stages of the visual pathway, including lens degeneration (bumper), melanin deficiency (sandy), lack of ganglion cells (lakritz), ipsilateral misrouting of axons (belladonna), optic-nerve disorganization (grumpy and sleepy), inner nuclear layer or outer plexiform layer malfunction (noir, dropje, and possibly steifftier), and disruption of retinotectal impulse activity (macho and blumenkohl). Surprisingly, mutants with abnormally large or small eyes or severe wiring defects frequently exhibit no discernible behavioral deficits. In addition, we identified 13 blind mutants that display outer-retina dystrophy, making this syndrome the single-most common cause of inherited blindness in zebrafish. Our screen showed that a significant fraction (approximately 5%) of the essential loci also participate in visual functions but did not reveal any systematic genetic linkage to particular morphological traits. The mutations uncovered by our behavioral assays provide distinct entry points for the study of visual pathways and set the stage for a genetic dissection of vertebrate vision.