| First Author | Gehrig A | Year | 2007 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 48 |
| Issue | 2 | Pages | 891-900 |
| PubMed ID | 17251492 | Mgi Jnum | J:123330 |
| Mgi Id | MGI:3717994 | Doi | 10.1167/iovs.06-0641 |
| Citation | Gehrig A, et al. (2007) Genome-wide expression profiling of the retinoschisin-deficient retina in early postnatal mouse development. Invest Ophthalmol Vis Sci 48(2):891-900 |
| abstractText | PURPOSE: The Rs1h knockout mouse displays retinal features typical for X-linked juvenile retinoschisis (RS). Consequently, this mouse line represents an excellent model to study early molecular events in RS. METHODS: Whole genome expression profiling using DNA-microarrays was performed on total RNA extracts from retinoschisin-deficient and wild-type murine retinas from postnatal days 7, 9, 11, and 14. Quantitative real-time RT-PCR (qRT-PCR) analysis of additional time points facilitated the refinement of the temporal expression profile of differentially regulated transcripts. Differential protein expression was confirmed by Western blot analysis. RESULTS: Based on biostatistic and knowledge-based DNA-microarray analyses we have identified differentially regulated retinal genes in early postnatal stages of the Rs1h-deficient mouse defining key molecular pathways including adhesion, cytoskeleton, vesicular trafficking, and immune response. A significant upregulation of Egr1 at P11 and several microglia/glia-related transcripts starting at P11 with a peak at P14 were identified in the diseased retina. The results provided evidence that macrophage/microglia activation precedes apoptotic photoreceptor cell death. Finally, the role of Egr1 in the pathogenesis of Rs1h-deficiency was investigated, and the results indicated that activation of the MAPK Erk1/2 pathway occurs as early as P7. Analyses of Rs1h(-/Y)/Egr1(-/-) double-knockout mice suggest that Egr1 upregulation is not a prerequisite for macrophage/microglia activation or apoptosis. CONCLUSIONS: The findings imply that microglia/glia activation may be triggering events in the photoreceptor degeneration of retinoschisin-deficient mice. Furthermore, the data point to a role of Erk1/2-Egr1 pathway activation in RS pathogenesis. |
