CLONING AND SEQUENCE-ANALYSIS OF THE MURINE GLUCAGON RECEPTOR-ENCODING GENE

The glucagon receptor (GR) plays a central role in regulating the level of blood glucose by controlling the rate of hepatic glucose production and insulin secretion. To study the integrated role of a candidate gene such as GR in whole-body glucose homeostasis by molecular genetic manipulation, cloning of the gene is required. We have cloned and sequenced the murine GR cDNA, gene and promoter region, and studied its tissue distribution. Murine GR contains 13 exons which are located in a region of 4.0 kb. GR encodes a 485-amino-acid protein that consists of seven putative transmembrane domains. By RT-PCR analysis, we have determined that GR is expressed predominantly in liver, kidney, adrenal, lung and stomach, while lower levels of expression are detected in brown and white adipose tissue, cerebellum, duodenum and heart. In addition, a 1000-bp region of the GR promoter has been sequenced which contains consensus sequences for putative DNA-binding proteins involved in tissue specificity (c/EBP; HNFI) or hormonal regulation (steroid receptor). Other consensus sequences known to function in controlling basal promoter activity, such as AP1, AP2 and Sp1, are also present. Conversely, no evident TATA or CAAT boxes are present. We provide here important new information necessary for the future pursuit of genetic manipulations in the mouse.