Cloning of a novel G-protein-coupled receptor GPR51 resembling GABA(B) receptors expressed predominantly in nervous tissues and mapped proximal to the hereditary sensory neuropathy type 1 locus on chromosome 9

Query of the expressed sequence tag database with the rat metabotropic GABA (B)R1A receptor amino acid sequence using the TFASTA algorithm revealed two partial cDNA fragments whose sequence information was then used to isolate by PCR a novel full-length human cDNA encoding a putative G-protein-couple d receptor (G;PCR), termed GPR 51. Sequence analysis revealed that it encod ed a protein of 941 amino acids, similar in size and homology to GABA(B) re ceptors followed by metabotropic glutamate receptors but not other GPCRs. G PR 51 expressed in COS-l cells showed no specific binding for [H-3](+)baclo fen and when expressed in Xenopus oocyte and Xenopus melanophore functional assays showed no activity to GABA, (-)baclofen, and glutamic acid. Norther n blot analysis and in situ hybridization revealed that GPR 51 transcripts were predominantly expressed in the central nervous system with highest abu ndance in the cortex, thalamus, hippocampus, amygdala, cerebellum, and spin al cord. In contrast, GPR 51 receptor transcripts were almost not detected in the peripheral tissues. Gene GPR 51 was localized by radiation hybrid ma pping to chromosome 9, 4.81 cR from the WI-8684 marker, and proximal to the hereditary sensory neuropathy type 1 locus, (C) 1999 Academic Press.