THE HUMAN BETA-SUBUNIT OF ROD PHOTORECEPTOR CGMP PHOSPHODIESTERASE - COMPLETE RETINAL CDNA SEQUENCE AND EVIDENCE FOR EXPRESSION IN BRAIN

We have identified and sequenced cDNA clones that encode for the human β-subunit of rod cGMP phosphodiesterase (PDEB). A single 2565-bp open reading frame that codes for an 854-amino-acid protein was identified. The human β-subunit protein is 90% identical to the bovine β-subunit and 91% identical to the mouse protein. Northern blot analysis indicates that the gene is expressed as an abundant 3.5-kb transcript in retina and as a rare 2.9-kb transcript in brain. The isolation of cDNAs from human brain cDNA libraries confirms the brain as a site of expression for this gene. The molecular defect underlying retinal degeneration in the rd mouse has been found to be a nonsense mutation in the β-subunit of the mouse cGMP PDE, resulting in a truncated protein (Pittler et al., 1991b, Proc. Natl. Acad. Sci. USA. 88: 8322-8326). The molecular cloning of the cDNA encoding for the PDEB represents the first step in establishing whether this gene plays a causative role in any one of the several human hereditary retinopathies or, based on its localization to chromosome 4p16.3, in the pathogenesis of Huntington disease. © 1992.