Microarray Analysis of Gene Expression Changes During Improvement of Schisis in Rs1tmgc1 Mice

Abstract

Purpose: : X-linked retinoschisis (XLRS) is an inherited form of macular degeneration that is caused by mutations in the retinoschisis 1 (RS1) gene. A major feature of this disease is splitting (schisis) of the retina. Previously, we reported that schisis phenotype in a mouse model of XLRS, the Rs1^tmgc1 mouse, becomes milder as the mice age. The purpose of this study is to identify transcriptional changes that occur during the natural recovery of schisis.

Methods: : RNA samples extracted from the retina of Rs1^tmgc1 mice at 5 weeks and 16 weeks of age were used to generate cRNA probes for hybridization to Affymetrix mouse genome arrays. After pre-analysis processing of the data, a t-test was performed to identify differentially expressed genes. We used the DAVID Functional Annotation Tool to identify enriched gene ontology terms.

Results: : We found that 103 genes were significantly up-regulated, and 258 genes were significantly down-regulated at 5 weeks old relative to 16 weeks old (>2 fold change). Among differentially expressed genes, the following are of particularly interest. (1) Expression of the collagen type IV alpha3, which may be associated with cell adhesion, is up-regulated at 16 weeks (average fold change 4.65). (2) One of the down-regulated genes is in the minimal genetic region of the Modifier of Rs1 (Mor1) gene, the AKR allele of which rescues the schisis phenotype of Rs1^tmgc1 mice.

Conclusions: : This study demonstrated that gene expression profile changes occur during improvement of schisis in the retina of Rs1^tmgc1 mice. Some of these up- or down-regulated genes may be associated with the function of Rs1. The gene mapped within the Mor1 locus is a good candidate for the Mor1 gene.

Keywords: retinal adhesion • gene microarray • genetics