Transcription profiling by array of mouse retina from wild type and ERR-beta knock out strains

Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor ERR-beta as selectively expressed in rod photoreceptors. Overexpression of ERR-betainduces expression of rod-specific genes in retinas of both wildtype and in Nrl-/- mice, which lack rod photoreceptors. Mutation of ERR-beta results in dysfunction and degeneration of rods, while inverse agonists of ERR-beta trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERR-beta. ERR-betacoordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERR-beta activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERR-beta is a critical regulator of rod photoreceptor function and survival, and suggest that ERR-beta agonists may be useful in the treatment of certain retinal dystrophies. Affymetrix MOE430 microarrays were used to analyze the expression patterns of P21 mouse retinal tissues. The results were compared across the variable of Genotype, specifically ERR-beta knockout versus wildtype.