cDNA Sequence and Gene Locus of the Human Retinal Phosphoinositide-Specific Phospholipase-Cβ4 (PLCB4)

9 páginas, 5 figuras.-- et al.Defects in the Drosophila norpA (no receptor potential A) gene encoding a phosphoinositide-specific phospholipase C (PLC) block invertebrate phototransduction and lead to retinal degeneration. The mammalian homolog, PLCB4 , is expressed in rat brain, bovine cerebellum, and the bovine retina in several splice variants. To determine a possible role of PLCB4 gene defects in human disease, we isolated several overlapping cDNA clones from a human retina library. The composite cDNA sequence predicts a human PLCβ4 polypeptide of 1022 amino acid residues (MW 117,000). This PLCβ4 variant lacks a 165-amino-acid N-terminal domain characteristic for the rat brain isoforms, but has a distinct putative exon 1 unique for human and bovine retina isoforms. A PLCβ4 monospecific antibody detected a major (130 kDa) and a minor (160 kDa) isoform in retina homogenates. Somatic cell hybrids and deletion panels were used to localize the PCLB4 gene to the short arm of chromosome 20. The gene was further sublocalized to 20p12 by fluorescence in situ hybridization.This research was supported by grants from the National Eye Institute (EY09123, EY00871, EY04149, EY07001), the RP Foundation Fighting Blindness (Baltimor, MD). and the Retina Research Foundation (Houston, TX).Peer reviewe