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MaryAnn Mahajan, Stephen H. Tsang, Jacqui K. White, Amir H. Assefnia, K.C. Kent Lloyd, Ramiro Ramirez-Solis, Vinit B. Mahajan; High-throughput Mouse Eye Phenotyping Reveals Novel Disease Pathways. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2352.
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To develop a high-throughput phenomics pipeline to identify novel candidate genes in mouse models of human ophthalmic disease.
A collaborative, scalable, horizontal infrastructure was created for high-throughput, remote acquisition and phenotyping of transgenic mouse eyes. Enucleated adult eyes and embryonic heads were processed for digital histology. Pupil-optic nerve sections were examined for abnormalities in the cornea, angle, iris, lens, ciliary body, vitreous, retina, retinal pigment epithelium, and optic nerve. Some eyes from targeted gene-trap lines were also examined for cellular expression of the lacZ reporter gene.
Over 1300 mouse eyes were screened. These included eyes from common wild type strains, 260 different transgenic lines, and 20 lacZ expressing lines. Phenotypic abnormalities were identified in 14 transgenic lines showing photoreceptor degeneration, retinal neovascularization, persistent fetal vasculature, corneal opacity, RPE macromelanosomes, microophthalmia, globe dysmorphology, orbital malformation, and cranial nerve hypoplasia. Expression of lacZ was observed in photoreceptors, corneal epithelium, and subsets of retinal ganglion cells. The corresponding gene functions included metabolic enzymes, ion exchangers, growth factors, transcription factors, and intracellular signal transduction molecules.
Transgenic mice produced in large consortiums and individual laboratories are a key resource for identifying important new animal models and new candidate genes for human eye disease. Our collaborative, tissue-sharing platform achieves high-throughput, low-cost phenotype discovery with immediate genotype correlation.
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