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Jiyao Zhu, Judy M Ogilvie; Differential gene expression in developing rd1 mouse retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):578. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is an inherited eye disease that can cause the night blindness, loss of peripheral vision, and eventually blindness. The rd1 mouse is a well-characterized animal model of RP with an early onset photoreceptor degeneration starting at postnatal day 10 (P10) and completion of rod photoreceptor cell death by P21. Previous studies have revealed that the rd1 mutant gene, Pde6b, is expressed embryonically in the mouse retina (Bibb, 2001) in contrast to other phototransduction genes that are expressed around P5. We hypothesize that Pde6β could play a role in retinal development independent of its function in phototransduction, contributing to differential gene expression prior to onset of rod cell death.
Retinal samples were harvested at either P4 or P6 from wild type or rd1 mice. Each sample was comprised of two retinas isolated from one male mouse pup. Replicates were harvested from littermates. Eight samples have been run for RNA-Seq data: isolated retinas from 2 different time points (P4 and P6) for both wild type and rd1 mutant retinas, 2 replicates of each condition. Differential gene and transcript expression analysis of RNA-Seq data were performed according to Tuxedo Protocol. Gene Ontology was used for functional enrichment analysis.
Results were compared to our previous microarray analysis of differential expression at the same time points (Dickison, 2012). RNA-Seq analysis identified 1616 differentially expressed genes in rd1 retinas at P4 and P6 compared to 77 genes identified by microarray analysis, confirming previous studies of the increased sensitivity of RNA Sequencing. Gene ontology annotation profiles of RNA-Seq data indicate that one third of these genes are involved in development. Quantitative real time PCR validated the RNA-Seq expression profile.
Our results are consistent with our hypothesis that early molecular changes in rd1 mouse leads to differential expression of genes related to development prior to onset of photoreceptor degeneration. Further molecular pathway analysis will allow identification of novel pathways linking phosphodiesterase signaling to rod photoreceptor cell degeneration.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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