CDNA SEQUENCE AND GENE LOCUS OF THE HUMAN RETINAL PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE-C-BETA-4 (PLCB4)

Defects in the Drosophila norpA (no receptor potential A) gene encodin g a phosphoinositide-specific phospholipase C (PLC) block invertebrate phototransduction and lead to retinal degeneration. The mammalian hom olog, PLCB4, is expressed in rat brain, bovine cerebellum, and the bov ine 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 p redicts a human PLC beta 4 polypeptide of 1022 amino acid residues (MW 117,000). This PLC beta 4 variant lacks a 165-amino-acid N-terminal d omain characteristic for the rat brain isoforms, but has a distinct pu tative exon 1 unique for human and bovine retina isoforms. A PLC beta 4 monospecific antibody detected a major (130 kDa) and a minor (160 kD a) isoform in retina homogenates. Somatic cell hybrids and deletion pa nels were used to localize the PCLB4 gene to the short arm of chromoso me 20. The gene was further sublocalized to 20p12 by fluorescence in s itu hybridization. (C) 1995 Academic Press, Inc.