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K. Schaeferhoff, S. Michalakis, N. Rieger, B. Wissinger, B. Chang, M. Biel, O. Riess, M. Bonin; Combined mrna and mirna Expression Profiling of the Cpfl1 Mouse - A Mouse Model of Cone Dystrophies. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5989.
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© ARVO (1962-2015); The Authors (2016-present)
The cpfl1 mutant (cone photoreceptor function loss 1) is a mouse model carrying mutations in the cone specific phosphodiesterase 6 (Pde6c). The phenotype is characterized by a loss of cone photoreceptor function and a fast, progressive degeneration of the cones. To investigate the biological events leading to the loss of photoreceptors we combined mRNA expression analysis with whole genome miRNA expression profiling.
Expression analysis of Cpfl1 and wildtype retinas was performed using Affymetrix MOE 430 2.0 microarrays. miRNA expression profiling was conducted on an Illumina whole genome Universal Bead Array. Differential regulated transcripts with a minimum change in expression level of 1.5 fold (p-value <0.05) were obtained and gene regulation networks were generated by the Ingenuity Pathways Analysis software. Data was verified via qRT PCR and immunohistochemistry. The study was performed in accordance with the ARVO Statement for the use of Animals in Ophthalmic and Visual Research.
338 transcripts were differentially regulated in the retinas of 4 week old Cpfl1 animals. A large number of genes encoding proteins involved in phototransduction were down regulated. A strong up regulation of Stat3 signaling was detected that could be verified by qRT PCR and immunohistochemistry. In the miRNA array analysis of 4 week old mice we found two significant regulated miRNAs which have potential target genes included in the differential transcript list of our microarray analysis. Among these are calcium dependent proteins and phosphodiesterase 1.
Expression analysis of the Cpfl1 mouse highlighted a misregulation of the phototransduction cascade in accordance with the loss of visual function that characterizes the phenotype. Up regulation of Stat3 signaling indicates a rescue attempt of the degenerating photoreceptors. The combination of mRNA and miRNA expression profiling permits a closer monitoring of the neurodegenerative events in the retina occurring during the course of degeneration.
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