The mouse gene for the inducible G-protein-coupled receptor edg-1

Edg-1, an immediate-early gene induced during the in vitro differentiation of human endothelial cells, encodes a G-protein-coupled receptor (GPR) that signals via the G(i)/mitogen-activated protein kinase (MAP kinase) pathway (Lee, M.-J., Evans, M., and Hla, T. (1996) J. Biol. Chem. 271, 11272-11279). It is a prototypical member of the subfamily of ''orphan'' receptors that are expressed in the cardiovascular and nervous systems. In this report, the mouse edg-1 gene was cloned and sequenced, and its expression patterns were defined. The edg-1 transcript was expressed in a wide variety of adult tissues including the brain, lung, liver, heart, and spleen. However, during embryogenesis, the edg-1 mRNA was induced late in development (after Embryonic Day 15.5) at centers of ossification. As a first step toward understanding the molecular basis of tissue-specific and inducible expression, the mouse edg-1 gene and its promoter were characterized. The mouse edg-1 gene is composed of two exons and is 4.9 kb in length. The second exon is large and contains the entire coding region and the 3'-untranslated region. The edg-1 promoter is TATA-less and contains GC-rich elements, and transcription initiation occurs from a single start site. The 5'-flanking region of the promoter contains several enhancer elements. However, the activity of the 5'-flanking region was suppressed by the repressor activity within the first intron. These data provide the basis for the further characterization of the regulation of the orphan GPR edg-1. (C) 1997 Academic Press.