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P.M. Nishina, K.L. Seburn, NMF Staff, W.N. Frankel; Screening for Ocular Mutants in the Neuroscience Mutagenesis Facility (NMF) at The Jackson Laboratory . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4528.
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Purpose: With the exception of trauma and infectious diseases, the majority of reported eye diseases are genetic in nature. While some of these eye diseases are associated with animal models, many exist for which we do not have models (e.g. OMIM, MGD, Retnet). A query of the database Online Mendelian Inheritance in Man, using "eye disease" as an identifier, yields 209 hits. The same query in Mouse Genome Database (MGD) yields 133 hits, 76 of which represent actual animals models with ocular abnormalities. Therefore, there are far more heritable diseases in humans that have been recorded than available as mouse models. The Jackson Laboratory has established a Neuroscience Mutagenesis Facility to produce new mouse models of human neurological disease. Within the vision domain, we are screening for models with ocular developmental anomalies as well as for degenerative disease. Methods: C57BL/6 mice are mutagenized with ethyl nitrosourea and 8,000 G3 mice will be screened by indirect ophthalmoscopy and by slit lamp biomiscroscopy per year. A cohort of ~1400 mice will also be tested by ERG and aged to 1 year, then rescreened. Results: Of 276 families tested thus far, 83 families were observed to have one phenodeviant and 23 with more than one phenodeviant. Abnormalities observed thus far include mice with corneal scarring, anterior segment abnormalities, open pupil, hyaloid remnants, and retinal spots. Heritability testing and mapping is currently underway. Confirmed mutants will be described in greater detail. Conclusions: Animal models are important to allow for identification of the molecular basis of disease and for elucidation of pathways in which particular genes function and to serve for testing therapeutic interventions. They are also especially important in eye research for providing much needed tissue to study pathological progression of disease and to study and, ultimately, understand normal eye biology. Mutagenesis programs have the potential for providing these much needed animal models.
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