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Robert C. Symons, Hongmei Niu, Bliss E. O'Bryhim; Identification of Genes and Pathways Associated with Differential Retinal Responses to Hypoxia in the Mouse Oxygen Induced Retinopathy Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3976.
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The retinal transcriptional response to hypoxia in the oxygen induced retinopathy (OIR) model was compared between BALB/cByJ and C57BL/6ByJ mice. BALB/c mice are less susceptible to vaso-obliteration in the OIR model than are C57BL/6 mice, and revascularize faster than C57BL/6 mice in the hypoxic phase of the model.
Total retinal RNA was isolated at P13 from mice from three different litters of each strain from both control mice and mice exposed to the OIR model. Gene expression was compared between control and experimental mice and between the two strains. Gene set enrichment analysis was used to identify gene-ontology categories and biological pathways that showed differential regulation between the strains. Changes in expression of selected genes were confirmed by quantitative rtPCR.
The expression of 69 gene transcripts was significantly altered in C57BL/6ByJ mice exposed to OIR compared to normoxic controls. These data were similar to those published by others profiling gene expression of C57BL/6N mice exposed to hyperoxia at P12. The expression of 65 genes was significantly altered in BALBC/cByJ experimental mice. Comparing experimental mice between strains showed significant alteration of 55 genes. Gene Set Enrichment Analysis (GSEA) of Kegg-defined pathways revealed up-regulated expression of genes related to cell communication and extracellular matrix receptor interaction in C57BL/6ByJ mice exposed to OIR compared to BALB/cByJ. The results of quantitative rtPCR were in agreement with the microarray data.
Compared with BALB/c, C57BL/6 are more susceptible to vaso-obliteration in response to hyperoxia, and their subsequent revascularization is slower. Alterations in gene expression may determine the differential response between these strains to murine OIR.
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