期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：25
页码：11579-11584
DOI：10.1073/pnas.1000102107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor estrogen-related receptor {beta} (ERR{beta}) as selectively expressed in rod photoreceptors. Overexpression of ERR{beta} induces expression of rod-specific genes in retinas of wild-type as well as Nrl-/- mice, which lack rod photoreceptors. Mutation of ERR{beta} results in dysfunction and degeneration of rods, whereas inverse agonists of ERR{beta} trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERR{beta}. ERR{beta} coordinates 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.
关键词：Crx ; ligand ; neurodegeneration ; retina ; development
