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A. S. Jelcick, J. Reinecke, Y. Yuan, N. B. Haider; The Influence of MicroRNAs on Nr2e3 Associated Retinal Disease in the rd7 Mouse Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4032.
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The variability of expression genes can contribute to the observed phenotype both a positive and negative manner. Micro RNAs (miRNA) influence gene expression by negative regulation. The purpose of this study is to examine the effect of microRNAs on Nr2e3 associated retinal disease. Nr2e3 is a crucial factor for proper photoreceptor development and function. Lack of Nr2e3 in patients is associated with enhanced S-cone syndrome and retinitis pigmentosa and in a superfluous production of blue opsin expressing cone cells and a slow progressive retinal degeneration as observed in the rd7 mouse model. We examine the influence of miRNAs on Nr2e3 associated retinal degeneration by comprehensive gene expression profile in the developing and mature rd7 retina.
microRNA was collected from embryonic (E) 18, P2, P6, P14, and P30 B6 (control) and rd7 retinas. microRNA samples were hybridized to mirVana miRNA chips. Initial normalization and analysis of miRNA expression data was performed using BRB ArrayTools. Subsequent analysis to determine statistically significant miRNA’s was performed using Stanford Array Tool’s SAM software. microRNA gene expression differences were confirmed by quantitative real time PCR.
Initial filtering, normalization and organization of miRNA’s expressed revealed 1981 miRNA’s to be expressed across B6 and rd7 samples. A subset of over 200 miRNA’s were entered into the SAM analysis software and statistically significant miRNA’s found to be differentially expressed across time points were also evaluated. Of the genes confirmed to be differentially expressed, it was observed that the target genes belonged to multiple families with multiple functions.
Differential expression of microRNAs were observed in B6 versus rd7 retinas and thus may contribute to retinal degeneration in these mice. Further pathway analysis will shed additional light on the possible functions of the genes regulated by these miRNAs, but initial analysis shows their involvement in regulation of genes encoding f-box proteins, nuclear receptors, and genes encoding for various types of ECM related fibers.
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