Over the next 5 years, the main objective of this project will be to isolate and analyze specific visual system mutations in zebrafish. Mutations are induced in zebrafish by exposing males to ethylnitrosurea, and recessive mutations are looked for in third-generation fish bred from second-generation siblings. Visual defects are detected using an optokinetic response test, i.e., the ability of the eye to follow a moving striped pattern.
Four specific aims are proposed: (1) to produce mutant fish that have a variety of visual system defects of interest to many visual system researchers; as mutant fish are uncovered and classified, these fish will be made available to interested parties; (2) to develop more sophisticated behavioral tests that will enable the uncovering of mutants specific to the visual system; in particular, behavioral tests that uncover visual system mutants in animals that are morphologically normal will be sought; (3) to analyze selected mutants at a cellular and molecular level in order to uncover ultimately the specific gene mutated, its protein product and the role of the gene and its product in retinal function, employing electrophysiological as well as cellular and molecular biological techniques initially to analyze these mutants; and (4) to continue studies on normal (wild-type) retinal structure, function and development in zebrafish as background for the analysis of mutant fish.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY000811-26
Application #
2019378
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Project Start
1976-12-01
Project End
2001-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
26
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
071723621
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
Moyano, Miguel; Porteros, Angel; Dowling, John E (2013) The effects of nicotine on cone and rod b-wave responses in larval zebrafish. Vis Neurosci 30:141-5
Li, Yong N; Tsujimura, Taro; Kawamura, Shoji et al. (2012) Bipolar cell-photoreceptor connectivity in the zebrafish (Danio rerio) retina. J Comp Neurol 520:3786-802
Le, Hong-Gam T; Dowling, John E; Cameron, D Joshua (2012) Early retinoic acid deprivation in developing zebrafish results in microphthalmia. Vis Neurosci 29:219-28
Hensley, Monica R; Emran, Farida; Bonilla, Sylvia et al. (2011) Cellular expression of Smarca4 (Brg1)-regulated genes in zebrafish retinas. BMC Dev Biol 11:45
Stujenske, Joseph M; Dowling, John E; Emran, Farida (2011) The bugeye mutant zebrafish exhibits visual deficits that arise with the onset of an enlarged eye phenotype. Invest Ophthalmol Vis Sci 52:4200-7
Emran, Farida; Rihel, Jason; Adolph, Alan R et al. (2010) Zebrafish larvae lose vision at night. Proc Natl Acad Sci U S A 107:6034-9
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
Emran, Farida; Rihel, Jason; Dowling, John E (2008) A behavioral assay to measure responsiveness of zebrafish to changes in light intensities. J Vis Exp :
Kojima, Daisuke; Torii, Masaki; Fukada, Yoshitaka et al. (2008) Differential expression of duplicated VAL-opsin genes in the developing zebrafish. J Neurochem 104:1364-71

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