RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the adult retina

The locus control region (LCR) of the human red and green visual pigment ge nes is critical for the formation of functional red and green cones in the retina. A 37-bp core of the LCR is perfectly conserved among mammals and bi nds specific retinal nuclear proteins. Here, we employed a yeast one-hybrid screen of an adult retinal cDNA library to clone and characterize these pr oteins. We identified clones encoding homeodomain (HD) transcription factor s Pax6, Rx, and Chx10 and a novel paired-like HD protein, RINX. In the adul t retina, RINX is exclusively expressed in a subset of cells (likely to be bipolar cells) of the retinal inner nuclear layer (INL). RINX is closely re lated to Chx10, which is also exclusively expressed in the INL of the adult retina and is critical for retinal development. The RINX gene is expressed in two classes of mRNA. One class encodes proteins that lack either part o f or all of the HD, but retain the transcriptional activation domain. The R INX gene maps to chromosome 20p11.2 to which no retinal disease has been as signed. In conclusion, the LCR contains two adjacent motifs that are target s for binding of HD proteins that may specify the development and different iation of cone photoreceptors and a subset of INL bipolar cells. Mutations in the related human CHX10 gene cause microphthalmia in a subset of familie s, and, therefore, the RINX gene is a candidate for this phenotype in anoth er subset of patients. Since the RINX gene is likely an ortholog of the gol dfish Vsx1 gene, it has been named VSX1 by the Human Gene Nomenclature Comm ittee. (C) 2000 Academic Press.