The locus control region (LCR) of the human red and green visual pigment genes 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 binds specific retinal nuclear proteins. Here, we employed a yeast one-hybrid screen of an adult retinal cDNA library to clone and characterize these proteins. We identified clones encoding homeodomain (HD) transcription factors Pax6, Rx, and Chx10 and a novel paired-like HD protein, RINX. In the adult 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 related 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 of or all of the HD, but retain the transcriptional activation domain. The RINX gene maps to chromosome 20p11.2 to which no retinal disease has been assigned. In conclusion, the LCR contains two adjacent motifs that are targets for binding of HD proteins that may specify the development and differentiation of cone photoreceptors and a subset of INL bipolar cells. Mutations in the related human CHX10 gene cause microphthalmia in a subset of families, and, therefore, the RINX gene is a candidate for this phenotype in another subset of patients. Since the RINX gene is likely an ortholog of the goldfish Vsx1 gene, it has been named VSX1 by the Human Gene Nomenclature Committee.
Copyright 2000 Academic Press.