Excess cones in the retinal degeneration rd7 mouse, caused by the loss of function of orphan nuclear receptor Nr2e3, originate from early-born photoreceptor precursors

• DOI: 10.1093/hmg/ddr334
• Publication Date: 2011-08-04T00:57:49Z
• Authors: H. Cheng; N. W. Khan; J. E. Roger; A. Swaroop
• Keywords: Degeneration (medical); Loss function; Orphan receptor

The orphan nuclear receptor NR2E3 is a direct transcriptional target of NRL, the key basic motif leucine zipper transcription factor that dictates rod versus cone photoreceptor cell fate in mammalian retina. lack function humans and retinal degeneration rd7 mutant mouse leads to increased S-cones accompanied by degeneration, whereas ectopic expression Nr2e3 cone-only Nrl−/− retina generates rod-like cells do not exhibit any visual function. Using GFP tag newborn rods 5-bromo-2′-deoxyuridine birthdating, we demonstrate early-born post-mitotic precursors express cone-specific genes. Transgenic studies background show when expressed under control Crx promoter can restore suppress gene expression. Furthermore, committed be (driven Nrl promoter) could completely rescue phenotype mice. We conclude excess originate from with 'default' proliferation cones required S-cone genes during normal differentiation. These further support 'transcriptional dominance' model determination provide insights into pathogenesis disease phenotypes caused mutations.