Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors.

PURPOSE: To characterize orthologous human and murine cDNAs isolated through separate screens designed to identify genes expressed preferentially in retina.
METHODS: By screening bovine, murine, and human retinal cDNA libraries, human UNC-119 clones of two varieties and a murine cDNA clone corresponding to the most abundant human transcript were isolated. Northern blot and reverse transcription-polymerase chain reaction analyses were used to determine tissue distribution of UNC-119 expression; in situ hybridization localized it in retina to photoreceptors. Fluorescence in situ hybridization was used to map the human structural gene, and its intron- exon boundaries were elucidated by polymerase chain reaction amplification and sequencing genomic DNA.
RESULTS: UNC-119 was expressed at high levels in photoreceptors and at low levels elsewhere. The most abundant transcript encoded a protein of 240 amino acids with homology to Caenorhabditis elegans UNC-119. Rat and human cDNAs of UNC-119 have been previously reported as human retinal gene 4 and rat retinal gene 4 (HRG4 and RRG4). An alternative splice form in humans arose from retention of the 3'-most intron, seemed to be retina-specific, and encoded a protein of 220 amino acids. The human structural gene mapped to 17q 1.2 and comprised at least five exons and four introns. A patient with neurofibromatosis type 1, which also maps to 17q11.2, and cone-rod dystrophy was examined for a deletion of UNC-119 but no abnormalities were found.
CONCLUSIONS: Given its strong degree of evolutionary conservation and abundant and nearly exclusive expression in photoreceptors, it is likely that UNC-119 plays an important role in vision and is a strong candidate gene for retinal diseases that map to 17q11.2.