Mutations of the Rhodopsin Gene in Zebrafish and uses of the Mutations

The invention involves isolation and use of zebrafish having novel genetic mutations in the rhodopsin genes dealing with retinal disease to serve as a model for human retinal disease. Rhodopsin is a protein receptor expressed in the light sensitive cells of the retina responsible for initiation of vision. Nearly 100 spontaneous mutations in the human rhodopsin genes are associated with inherited photoreceptor degeneration, retinitis pigmentosa, progressive retinal degeneration, low vision and blindness for which there are currently no cures. The novel zebrafish models were generated to produce known disease causing mutations in the zebrafish rhodopsin genes. DNA sequencing revealed the novelty of the isolated zebrafish mutations. Analysis of the retinal phenotypes associated with the novel alleles of zebrafish rhodopsin genes revealed that specific mutations were associated with phenotypes that mimic photoreceptor defects and degeneration observed in humans. These zebrafish models provide novel tools for investigating the cellular consequences of expression of mutated forms of rhodopsin, and are useful for genetic, small molecule, and chemical screens, or molecular manipulations with the goal of discovering compounds, genes, or treatments that may alter, slow, reverse or prevent the photoreceptor defects.