June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Retinal gene expression in mice lacking cones and/or rods identifies genes potentially involved in human eye function and disease
Author Affiliations & Notes
  • Richard Holt
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
  • Laurence Brown
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
  • Rachel Butler
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
  • Susan Downes
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Oxford Eye Hospital, National Health Service, Oxford, United Kingdom
  • Stuart Peirson
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
  • Stephanie Halford
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships Richard Holt, None; Laurence Brown, None; Rachel Butler, None; Susan Downes, Novartis (F); Stuart Peirson, None; Stephanie Halford, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1323. doi:
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      Richard Holt, Laurence Brown, Rachel Butler, Susan Downes, Stuart Peirson, Stephanie Halford; Retinal gene expression in mice lacking cones and/or rods identifies genes potentially involved in human eye function and disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1323.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Advances in sequencing have increased the potential to identify genetic variants in individuals with retinal disease; however determining which are causal remains a challenge. In order to generate a resource to help identify genes involved in retinal function, and so provide candidates for disease studies, we examined gene expression in retinae from 3 transgenic mouse strains; rd/rd (rodless), Cl (coneless) and rd/rdCl (rodless and coneless) and compared them to wild type.

Methods: Retinae were excised from rd/rd, Cl, rd/rdCl and wild type mice, and RNA extracted. cDNA for probes was generated using the Ambion® WT Expression Kit. Gene expression was examined using the GeneChip® mouse exon 1.0 ST arrays. Data was processed using AltAnalyze v2.0.7 and a Benjamini-Hochberg correction for multiple testing applied. qPCR validation was performed using the QuantiFast® SYBR® Green PCR kit. Clustering and pathway analysis was performed in Cytoscape v2.8. Gene set enrichment analysis was performed using GSEA v2.07.

Results: The expression of 27,966 genes was determined in retinae from each of rd/rd, Cl, rd/rdCl and wild type mice and compared between each transgenic strain and wild type. Clustering analysis was performed for all genes with a P <0.001 in at least one of the transgenic strains. Clustering was similar for rd/rd and rd/rdCl, but with a striking difference to Cl mice. Expected functions such as phototransduction were highlighted, but also revealed other functions such as cell projection and transferase activity. Human orthologues of many genes with the largest decreases in expression are involved in retinal disease, confirmed by gene set enrichment analysis (P <0.0001 for rd/rd, Cl and rd/rdCl). Comparison to human disease loci with unknown causal genes identified candidates with significant decreased expression demonstrating the utility of the data to aid identification of novel candidates.

Conclusions: We have generated catalogues of genes with decreased expression in mice lacking cones, rods or both. This provides information on new genes for investigation into the normal function of the eye, and will help determine genes involved in human retinal disease by identifying candidate genes in disease loci, or acting as a filter for high-throughput sequencing data.

Keywords: 533 gene/expression • 535 gene microarray • 648 photoreceptors  
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