This project is a collaboration between an ophthalmologist-clinician and a mouse geneticist in which clinically relevant mouse models of ocular disease are identified. The protocol for each newly discovered disorder is to confirm the genetic basis for the phenotype, to document the natural disease course by employing clinical and basic science methods, and to perform genetic studies to determine the mode of inheritance, possible allelism with known mutants, and chromosomal location. The proposal is focussed on screening strains maintained at the Jackson Laboratory in order to identify genes affecting visual function that may serve as models for human disorders. During the past five year funding period, 500 strains were screened and 44 mutant loci were identified. During the proposed 5 year period, the remaining 1,000 stocks will be screened, using some improved methods. Mutant loci will be chromosomally mapped using crosses to CAST/Ei and microsatellite typing of pooled DNA samples from affected animals. Retinal specific cDNAs will be genetically mapped, and transcripts of candidate genes located close to the mutant loci will be sequenced. An attempt will be made to focus on disorders associated with aging, since the majority of serious human eye problems occur in older individuals, and good models and better understanding of the genetics and pathological mechanisms of these disorders are needed. Comprehensive genetic studies and preliminary functional characterization will be performed at the Jackson Laboratory. Detailed analysis by electroretinography, histology and clinical characterization will be performed at Harbor/UCLA.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY007758-09
Application #
2019707
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1988-08-01
Project End
1999-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
City
Torrance
State
CA
Country
United States
Zip Code
90502
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