There is a great need for a systematic approach to identify and describe genetically-determined eye disorders in mice. First, there is significant value that experimental animal models of human eye conditions can bring to human ocular research. Our preliminary screening of mouse colonies, strains and mutant stocks at the Jackson Laboratory, using modified clinical techniques including electroretinograms, revealed a large number of mouse ocular abnormalities heretofore not known or well characterized, which have special relevance to human disorders. These include slow and fast retinal degenerations, corneal dystrophy and dysgenesis, dominant and recessive cataracts, persistent hyperplastic primary vitreous, Peter's anomaly, posterior staphyloma, optic atrophy, micro-ophthalmia, and possibly macular degeneration (degeneration with drusen). Second, there is an exceptionally high genetic homology between human and mouse genomes permitting accurate prediction of mapping locations of human ocular diseases from our knowledge of mapping the homologousloci in mouse. Five loci have been mapped for the first time in this study with mapping experiments underway with several others. Since only a portion of the 1500 or so Jackson stocks have been evaluated, and since new mutations regularly are found among the large animal colonies, it is expected that many more important ocular models will come to light. Furthermore, upon initial characterization of the clinical and genetic features of these mutations, there is a mechanism in place to maintain and distribute animals to the research community. The methodology calls for a true partnership between a clinician/ophthalmologist and a mouse geneticist/mapping expert. The protocol includes the continual screening of large numbers of strains and mutants by biomicroscopy, indirect ophthalmoscopy and ERG. Along with clinical characterization of disorders, studies of genetic etiology and mapping are being done. The uniqueness of each disorder, thus will be confirmed by breeding experiments and linkage analysis. Publications of findings will be made so that disorders are known and made available immediately to other researchers. Further in-depth studies will be done in our laboratories specifically on retinal disorders and in the laboratories of other interested collaborators.
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