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K. M. Malanson, Z. Cao, N. A. Panjwani, J. Lem; Involvement of Glyco-Genes in the P347S Mouse Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4086.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies reveal a role for the sugar-binding galectin proteins in the degeneration of neuronal processes (Plachta et al 2007, Chang-Hong et al 2005, Sakaguchi et al 2006, Ishibashi et al 2007, Kajitani et al 2009, Jin et al 2007). These results suggest the possibility that alterations in glyco-genes, which are carbohydrate-binding proteins, glycosyltransferases, and other genes involved in the regulation of glycosylation, may play a role in retinal degeneration, an area that is relatively unexplored. This study examines the involvement of glyco-genes, specifically galectin-1, in the retinal degeneration observed in the P347S rhodopsin mutant mouse model of retinitis pigmentosa.
To identify differentially expressed glyco-genes in the P347S model of RP, we completed a glyco-gene array. Total RNA was isolated from P347S mutant and control retinas at 1, 2, 3 and 4 months of age. RNA was amplified and hybridized to the GLYCOv4 glyco-gene microarray that contains over 1,000 probes for carbohydrate binding proteins and other genes involved in glycosylation. Statistical analysis was completed to identify transcripts that are differentially expressed between P347S mutant and control retinas. Transcripts identified from the microarray were validated using quantitative PCR, immunoblots and immunohistochemistry.
Galectin-1 has been shown to be up-regulated in the P347S mutant retina compared to control at 2 and 3 months, both at the RNA and protein level. Additionally, galectin-1 has also been found to localize within the inner segment and plexiform layers of both the mutant and wild-type retina. Quantitative PCR has validated the up-regulation of CSF1 and CSF1-R in the P347S mutant retina compared to control at the 3 and 4 month time points.
Galectin-1, CSF1, and CSF1-R have increased expression in the P347S mutant retina compared to control. We are currently investigating the functional significance of this up-regulation.
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