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B. T. Martin, E. O. List, J. J. Kopchick, Y. Sauve, S. Harvey; Microarray Analysis of the Retina in Growth Hormone Transgenic Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3323.
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© ARVO (1962-2015); The Authors (2016-present)
Previous work in our lab using the electroretinogram has functionally characterized the bovine growth hormone expressing (bGH) mouse as having depressed oscillatory potentials (OPs) in comparison to wild-type (WT) littermates. A microarray analysis of the retina was performed to identify candidate genes contributing to this phenotype.
Total RNA was extracted from the retinas of 6 WT and 6 bGH mice by BioServe (Beltsville, MD). The expression level of 29,922 gene transcripts was measured using the Phalanx Biotech OneArray (Palo Alto, CA). Hierarchical clustering and functional gene-set analysis was performed on the resulting data to compare the retina of WT and bGH mice.
Gene-sets associated with Angiogenesis revealed 13 member genes in the retinas of bGH mice that had significant alterations (P<0.05) in their expression patterns in comparison with WT mice. Similarly, 52 genes associated with Apoptosis were altered, as were 8 genes associated with Diabetes, 12 with Neurotransmission, 10 with Neurotrophins, and 5 with the Janus-kinase (JAK) signalling pathway.In the Angiogenesis gene set for bGH mice, vascular endothelial growth factor (VEGF) receptor 2 precursor expression was increased to 134% of WT levels (P < 0.01), while VEGF-A precursor was increased to 123% of WT levels (P < 0.05). Pro-apoptotic transcripts of death-inducer obliterator 1 were reduced to 71% of WT levels (P < 0.01). Transcripts for 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, an enzyme important for glycolysis with involvement in diabetes, was upregulated to 146% of WT levels (P < 0.05). There were significant changes to members of neurotransmission and neurotrophic gene sets, including neuropeptide Y receptor type 2 (91% of WT levels, P < 0.01), ATP-sensitive inward rectifier potassium channel 12 (118%, P < 0.05), somatostatin receptor type 1 (91%, P < 0.05), and insulin-like growth factor-binding protein 6 precursor (79%, P < 0.005). Lastly, in the JAK pathway, suppressor of cytokine signaling 2 was upregulated to 154% of WT levels (P < 0.0001).
The results of this study indicate that the depressed OPs may result from impaired vascular or neural function, or that altered cell survival during development may have led to long-lasting changes in retinal gene transcription.
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