This project has focused on finding new mouse models of ocular disease, mapping and identifying the causative genes, and phenotyping the disorders. The project has been an ongoing, highly productive collaboration between an academic Ophthalmologist (subspecialty: ophthalmic genetics and retinal dystrophy) and clinical electrophysiologist at UCLA, and mammalian geneticists at the Jackson Laboratory (TJL). Our program discovers and characterizes new mouse models of ocular disease, which are clinically relevant to human eye diseases. Because there is high homology between the human and mouse genomes, estimated to be 90-95%, findings in mouse normally have a very high likelihood of having validity in human. Mouse models of inherited ocular disease allow for rapid genetic analysis, pathophysiologic characterization, and lead to a quicker understanding of disease processes. Models are important because human eye tissues are seldom available for studies in a reliable fashion. In the current grant period, we have found 22 new mouse models of eye disease [Table 1], identified three genes for retinal degeneration (rd10, rd12, cpf11), one gene (Vldlr, a targeted mutation) associated with subretinal and choroidal neovascularization (CNV), and three genes for cataracts (Lop12, Nm1853, Nm3062). We mapped 17 new eye mutant genes (Table 2) and 10 ocular cDNA clones (Table 3), published 18 papers and 12 abstracts. As of this renewal, this project has discovered 96 mouse models of ocular diseases, and mapped 52 of them to mouse chromosomes (see Appendix, Table 1), 44 of them have not yet been mapped (see Appendix, Table 2). One of the successful aims of our project has been to redesign human clinical testing techniques so that they can be applied to mouse, giving comparable data to human. We have successfully developed new techniques for electro-physiologic testing in mouse including a standardized cone and rod ERG, which is now widely used, multifocal ERG testing, sweep VECP for measuring visual acuity in mouse, and fundus photography and fluorescein angiography of mouse retina.
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