ENU-induced late-onset night blindness associated with rod photoreceptor cell degeneration in zebrafish.

We describe a dominant mutation, night blindness d (nbd), that causes late-onset rod photoreceptor cell degeneration in zebrafish. The mutation was induced by treating male zebrafish with N-ethyl-N-nitrosourea (ENU). Visual sensitivity was tested using a behavioral assay based on a visually mediated escape response. At a young age, the heterozygous (nbd+/-) fish did not show any signs of night blindness or retinal degeneration. At 2 years, their behaviorally assessed visual sensitivity was decreased, albeit no alterations in the electroretinogram (ERG) were detected. Histology revealed that in the mutant retinas the rod photoreceptor cell outer segments (ROS) were thinned out. In homozygous larvae (nbd-/-), mass neural degeneration was detectable at about 2 days post fertilization (dpf). They died at an early age, usually no later than 8 dpf. In conclusion, nbd is a dominant mutation that causes late-onset night blindness with slow progression. However, nbd is not photoreceptor cell-specific, as becomes clear from the systemic dysfunctions of the homozygous larvae.