A DOMINANT FORM OF INHERITED RETINAL DEGENERATION CAUSED BY A NON-PHOTORECEPTOR CELL-SPECIFIC MUTATION

We have isolated a dominant mutation, night blindness a (nba), that ca uses a slow retinal degeneration in zebrafish, Heterozygous nba fish h ave normal vision through 2-3 months of age but subsequently become ni ght blind, By 9.5 months of age, visual sensitivity of affected fish m ay be decreased more than two log units, or 100-fold, as measured beha viorally, Electroretinographic (ERG) thresholds of mutant fish are als o raised significantly, and the ERG b-wave shows a delayed implicit ti me, These defects are due primarily to a late-onset photoreceptor cell degeneration involving initially the rods but eventually the cones as well, Homozygous nba fish display an early-onset neuronal degeneratio n throughout the retina and elsewhere in the central nervous system, A s a result, animals develop with small eyes and die by 4-5 days postfe rtilization (pf), These latter data indicate that the mutation affecti ng nba fish is not in a photoreceptor cell-specific gene.