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P.M. Nishina, W. Hicks, M. McCluskey, K. Ishimura, J.K. Naggert; Screening for Ocular Mutants in G3 ENU Mutagenized Mice at the Jackson Laboratory . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4583.
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There are far more heritable retinal diseases reported in humans than there are animal models available to study these diseases. Additionally, a large number of genes are expressed in the retina, an "outpost" of the central nervous system, whose function is not fully understood. The Jackson Laboratory has established a mutagenesis program to produce new mouse models of human ocular diseases to address both of these shortcomings. Mice with ocular developmental anomalies as well as degenerative diseases are being identified.
C57BL/6 mice are mutagenized with ethyl nitrosourea (ENU) and mated to produce a G3 generation. The resulting G3 mice are aged to 24 weeks and screened by indirect ophthalmoscopy, by slit lamp biomicroscopy, and by ERG.
Some 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. Of the 10 models with proven heritability and which we have mapped, three were remutations of known genes; other loci appear to be novel. Confirmed mutants will be described in greater detail.
In the small cohort tested thus far, 50% of the mutants identified with interesting ocular phenotypes are proven to be reproducibly heritable. Of the heritable mutants, ∼30–50% are remutations of genes in which animal models exist and the remaining mutants appear to be novel. Animal models are important to allow for identification of the molecular basis of disease, for elucidation of pathways in which particular genes function, and for providing a resource in which to test therapeutic interventions. They provide an unlimited source of tissue to study pathological progression of disease and, ultimately, to understand normal eye biology. Mutagenesis programs have the potential for providing these much needed animal models.
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