The Uroguanylin Gene (Guca1b) Is Linked to Guanylin (Guca2) on Mouse Chromosome 4

Abstract

Uroguanylin is an endogenous ligand of the intestinal receptor guanylate cyclase-C (GC-C). Both uroguanylin and the related peptide ligand guanylin bind to GC-C and stimulate an increase in cyclic GMP, inducing chloride secretion via the cystic fibrosis transmembrane conductance regulator. We describe the cloning of the complete mouse uroguanylin gene (Guca1b) and show thatGuca1bis tightly linked to the mouse guanylin gene on chromosome 4. The two genes are structurally similar, being composed of three short exons; the uroguanylin gene spans 2.4 kb and the guanylin gene spans 1.7 kb. Uroguanylin mRNA is most prominent in proximal small intestine, whereas guanylin mRNA is predominantly expressed in distal small intestine and colon. The upstream promoter sequence of the mouse uroguanylin gene contains a canonical TATA element at the site of transcription initiation and consensus binding sites for several known transcription factors, including HNF-1 and Sp1 within the first 1 kb. Although the gene structure and coding sequences of uroguanylin and guanylin are similar, the 5′ flanking sequences and patterns of expression of these two genes in the intestine are different. It is likely that uroguanylin and guanylin represent gene duplications that have evolved to allow overlapping and complementary patterns of expression in the intestine.