A large number of genes have been implicated in the inherited retinal degeneration syndromes affecting human populations. In all but one of these cases, as well as in all existing animal models of retinal degeneration, the nature of the affected gene products is not known. The long term goal of this research program is to understand the cellular and molecular mechanisms involved in these syndromes. By investigating retinal degeneration in Drosophila melanogaster, elegant genetic and molecular techniques can be applied to this problem. This proposal concerns the molecular characterization of two genes involved in retinal degeneration. The first of these is ninaE, which due to its homology to vertebrate rhodopsins, we can infer the tertiary structure of the gene product. In-vitro mutagenesis as well as DNA sequence determination of existing mutants will delimit the importance of specific peptide regions to the function of this protein. The second gene is rdgP6. The rdgP6 mutation is unique among Drosophila mutants, and may prove to be a good model for vertebrate retinal degenerative diseases. No physiological effect of this gene is evident in degeneration that becomes severe in older flies. The experiments described here will examine the nature of the rdgP6 gene and gene product. This gene will be cloned by utilizing recently isolated P-factor induced alleles. The DNA sequence will be determined, and experiments will look for homologous genes expressed in the vertebrate retina. We will seek genetic and environmental conditions that either enhance or attenuate the rate of rdgP6 retinal degeneration. We will also continue our efforts to identify other Drosophila genes involved in retinal degeneration. These mutant stocks will allow an important contribution to our understanding of the molecular events involved in retinal degeneration processes.
