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Alejandra Young, Benjamin E. Reese, Novrouz Akhmedov, Debora B. Farber; Candidate Genes Critical for Normal Axonal Navigation at the Optic Chiasm of Oculocutaneus and Ocular albino Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6024.
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© ARVO (1962-2015); The Authors (2016-present)
To define the differential gene expression profiles associated with embryonic retinal cells from c2J and Oa1-/- mice(models forOculocutaneous and Ocular albinism, respectively) and their corresponding control mice (C57Bl/6 and NCrl),using microarray analysis. Since melanin biosynthesis plays an important role in the ipsilateral/contralateral decision of ganglion cell axons at the optic chiasm, clustering of the axonal guidance genes from control and diseased retinas hybridized differently in the microarrays will allow us to identify genes influencing normal/abnormal decussation at the chiasm and, directly or indirectly, RPE pigmentation.
12.5 dpc mouse embryos (7-13/litter) were collected from c2J, Oa1-/- and the corresponding (C57Bl/6 and NCrl) females. Total RNA was isolated from eyes of each litter and stored as one biological sample at -80ºC. Samples were hybridized to mouse Affymetrix gene arrays at the UCLA Microarray core facility. RT-PCR was used to confirm the differential expression of those genes involved in the Axon Guidance Pathway common to both c2J and Oa1-/- mice or specific to each of these animal models of albinism.
Analysis of the microarrays from Oa1-/- vs. control NCrl mice gave 37 significant, differentially expressed genes from which 7 were involved in axon guidance: 4 up-regulated and 3 down-regulated. Similarly, analysis of c2J vs. C57B6 samples gave 209 significant differentially expressed genes from which only 2 down-regulated genes were related to axon guidance. QPCR confirmed the differential expression of the selected axon guidance genes.
Microarray analysis of the RNA from 12.5dcp embryonic eyes of albino Oa1-/- and c2J mice, which have common visual abnormalities, and their corresponding control pigmented mice, has provided the first comprehensive list of genes potentially involved in normal/abnormal optic axon guidance. These genes may also influence normal melanogenisis and the abnormal pigmentation associated with oculocutaneous and/or ocular albinism.
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