The primary clinical symptoms of Usher syndrome are congenital hearing loss and retinitis pigmentosa, which often leads to total blindness. The benefits gained from studying the genetic defects responsible for the major cause of deaf-blindness cannot be underestimated. I propose to study the genetic components of Usher syndrome in zebrafish via a mutagenesis screen and further characterizing a previously identified Usher mutant zebrafish, mariner.
In Specific Aim 1, I will study the development of the mariner retina. Mariner zebrafish have mutations in the gene encoding Myosin VIIa which is responsible for Usher syndrome type 1B. The hearing deficits in these fish have been studied, but the eye has not been characterized. I will determine if there is a correlation between the eye morphology and physiological measurements obtained from electroretinograms (ERG). I will also examine the role of rhodopsin trafficking in mariner to determine if this is a mechanism responsible for rod degeneration.
In Specific Aim 2, I will conduct a chemical mutagenesis screen and isolate mutants with auditory and visual deficits by acoustic-vibrational startle reflex and optokinetic assays. Both morphological and physiological studies (e.g. ERG and auditory brain stem responses) will be used. Positional cloning strategies will be used to identify the genes responsible for these mutations.
