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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32EY014790-01
Application #
6646358
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Dudley, Peter A
Project Start
2003-05-01
Project End
2006-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$39,700
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Wasfy, Meagan M; Matsui, Jonathan I; Miller, Jessica et al. (2014) myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses. Exp Eye Res 122:65-76
Uribe, Phillip M; Asuncion, James D; Matsui, Jonathan I (2013) Ethanol affects the development of sensory hair cells in larval zebrafish (Danio rerio). PLoS One 8:e83039
Li, Yong N; Matsui, Jonathan I; Dowling, John E (2009) Specificity of the horizontal cell-photoreceptor connections in the zebrafish (Danio rerio) retina. J Comp Neurol 516:442-53
Song, Philip I; Matsui, Jonathan I; Dowling, John E (2008) Morphological types and connectivity of horizontal cells found in the adult zebrafish (Danio rerio) retina. J Comp Neurol 506:328-38
Matsui, Jonathan I; Egana, Ana L; Sponholtz, Todd R et al. (2006) Effects of ethanol on photoreceptors and visual function in developing zebrafish. Invest Ophthalmol Vis Sci 47:4589-97
Duncan, Luke J; Mangiardi, Dominic A; Matsui, Jonathan I et al. (2006) Differential expression of unconventional myosins in apoptotic and regenerating chick hair cells confirms two regeneration mechanisms. J Comp Neurol 499:691-701
Matsui, Jonathan I; Ryals, Brenda M (2005) Hair cell regeneration: an exciting phenomenon...but will restoring hearing and balance be possible? J Rehabil Res Dev 42:187-98
Matsui, Jonathan Isamu; Cotanche, Douglas Allen (2004) Sensory hair cell death and regeneration: two halves of the same equation. Curr Opin Otolaryngol Head Neck Surg 12:418-25