GSE29752
RNA-Seq of mouse eye and retina tissues from wild type and Nrl transcription factor knockout mice
The initial aim of this work was to understand the pathophysiology of Enhanced S-cone Syndrome (ESCS) that leads to retinal degeneration. Although ESCS was identified in humans decades ago and since then the causative genes have been elucidated, our understanding of the accompanying retinal degeneration is still poorly understood. Knockout of the Nrl transcription factor in mice produces a retina overpopulated with S-cone like photoreceptors along with absence of rod photoreceptors and recapitulates many of the phenotypic features seen in human ESCS patients. We wanted to study this murine model through a combinatorial genetic and structural approach to improve understanding of the disease process that leads to photoreceptor degeneration and blindness, potentially guiding future therapies. By using RNA-Sequencing (RNA-Seq) to examine mature wild type and Nrl-/- ocular tissues, we were able to determine global changes in their transcriptomes. The massively parallel RNA-sequencing experiment revealed new insight into the transcriptional mis-regulation in the ESCS murine model and revealed a change in gene expression in putative proteins involved in photoreceptor phagocytosis. Key photoreceptor ligands necessary for phagocyotsis, Tub and Tulp1, were down-regulated in the Nrl-/- retina. Down regulation of key retinoid metabolic genes, coupled with down-regulation of Tub and Tulp1, suggested a potential mechanism involving defective phagocytosis underlies the photoreceptor degeneration seen in ESCS. Overall design: We report RNA-Seq experiments of whole eye and retinal tissues from wild type and Nrl transcription factor knockout mice on the C57BL/6 background. Examine two different ocular tissues in two mouse models of varying photoreceptor populations