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 causes a slow retinal degeneration in zebrafish. Heterozygous nba fish have normal vision through 2-3 months of age but subsequently become night blind. By 9.5 months of age, visual sensitivity of affected fish may be decreased more than two log units, or 100-fold, as measured behaviorally. Electroretinographic (ERG) thresholds of mutant fish are also raised significantly, and the ERG b-wave shows a delayed implicit time. 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 degeneration throughout the retina and elsewhere in the central nervous system. As a result, animals develop with small eyes and die by 4-5 days postfertilization (pf). These latter data indicate that the mutation affecting nba fish is not in a photoreceptor cell-specific gene.

[1]  T. L. McGee,et al.  Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J B Hurley,et al.  A behavioral screen for isolating zebrafish mutants with visual system defects. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. J. Mullen,et al.  Two new types of retinal degeneration in cerebellar mutant mice , 1975, Nature.

[4]  E. Berson.  Retinitis pigmentosa. The Friedenwald Lecture. , 1993, Investigative ophthalmology & visual science.

[5]  J. Dowling.  The Retina: An Approachable Part of the Brain , 1988 .

[6]  A. Schier,et al.  A genetic screen for mutations affecting embryogenesis in zebrafish. , 1996, Development.

[7]  E. Berson,et al.  Olivopontocerebellar atrophy with retinal degeneration. An electroretinographic and histopathologic investigation. , 1993, Ophthalmology.

[8]  E. Berson,et al.  Prevalence of retinitis pigmentosa in Maine. , 1984, American journal of ophthalmology.

[9]  V. Sheffield,et al.  Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis. , 1991, American journal of human genetics.

[10]  P. Rivlin,et al.  Regeneration of goldfish retina: rod precursors are a likely source of regenerated cells. , 1988, Journal of neurobiology.

[11]  C. Nüsslein-Volhard,et al.  Neural degeneration mutants in the zebrafish, Danio rerio. , 1996, Development.

[12]  T. Dryja,et al.  Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. , 1994, Science.

[13]  J. Dowling,et al.  Comparison of topographical patterns of ganglion and photoreceptor cell differentiation in the retina of the zebrafish, Danio rerio , 1996, The Journal of comparative neurology.

[14]  H. Steller,et al.  Programmed cell death during Drosophila embryogenesis. , 1993, Development.

[15]  D A Kane,et al.  The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. , 1996, Development.

[16]  P. Rivlin,et al.  Germinal cells in the goldfish retina that produce rod photoreceptors. , 1987, Developmental biology.