A large number of retinal degeneration mutants have been generated in Drosophila. Analyzing these mutants have identified several key components of the visual transduction cascade and other critical cell biological components for the photoreceptor cell, which has led to models for the underlying degeneration mechanisms. This project will employ molecular, genetic, and cell biological approaches to examine the degeneration mechanisms associated with two different mutants. Dominant rhodopsin mutations are a major cause of one form of autosomal dominant retinitis pigmentosa in humans. Several mechanisms have been proposed for the retinal degeneration process. One class of dominant rhodopsin mutants was previously characterized in Drosophila and shown to undergo degeneration by blocking the maturation of the wild-type rhodopsin protein. We isolated two additional dominant rhodopsin mutations (ninaEpp36 and ninaEpp100 that exhibit retinal degeneration, but do not block rhodopsin maturation. Additionally, several lines of data strongly suggest that the ninaEpp36 and ninaEpp100 mutations utilize different mechanisms to produce the retinal degeneration phenotype. We will examine these underlying degeneration mechanisms to elucidate additional models for autosomal dominant retinitis pigementosa. The retinal degeneration G (rdgG) mutation exhibits a light-independent, temperature-sensitive retinal degeneration phenotype. The electrophysiological light response (measured by the electroretinogram) of the rdgG mutant is wild-type, except for the inability to dark recover after an extended saturating light stimulus. This suggests that the rdgG mutant may exhibit """"""""run-down"""""""" of a critical component in the visual transduction process.
|Iakhine, Roustem; Chorna-Ornan, Irit; Zars, Troy et al. (2004) Novel dominant rhodopsin mutation triggers two mechanisms of retinal degeneration and photoreceptor desensitization. J Neurosci 24:2516-26|
|Kosloff, Mickey; Elia, Natalie; Joel-Almagor, Tamar et al. (2003) Regulation of light-dependent Gqalpha translocation and morphological changes in fly photoreceptors. EMBO J 22:459-68|