CRP-DUCTIN - A GENE EXPRESSED IN INTESTINAL CRYPTS AND IN PANCREATIC AND HEPATIC DUCTS

BACKGROUND: A subtraction screen isolated CRP-ductin (CRP), a gene exp ressed in intestinal crypts. METHODS: DNA sequencing, in situ hybridiz ation, immunostaining, Western and Northern blotting were used to char acterize murine CRP. RESULTS: CRP is restricted to the intestine and i ts associated glands, In the small intestine, CRP mRNA is expressed in crypt cells at all stages of differentiation from the stem cells to t he terminally differentiating cells of the crypt top, but not in the m ature cells of the villus, In the colon, CRP mRNA is most heavily expr essed in the mid-crypt, Expression is also seen in the pancreas and pa ncreatic ducts, and in the epithelium lining larger hepatic ducts, but not in the Liver parenchyma or stomach, CRP protein is localized to t he lumenal aspect of crypt cells in the small intestine, In the colon, the protein is seen in the lumenal aspect of surface epithelial cells , CRP protein is similarly found in the lumenal aspect of epithelial c ells lining the pancreatic duct system and the larger hepatic ducts, T wo cDNA variants, CRP-alpha and CRP-beta, were cloned from mouse jejun al epithelium. Their 3'-sequence differs in an 82-bp domain unique to CRP-beta. CONCLUSIONS: The CRP-alpha sequence predicts a protein with a short cytoplasmic region, a transmembrane domain, and a large extrac ellular region composed of many repeats (8 scavenger receptor domains, 5 CUB-domains, 1 ZP-domain, and 6 copies of a previously unreported d omain which we call the CRP-domain). The structure of the CRP protein suggests a role in ligand interaction; possible functions are discusse d. (C) 1996 Wiley-Liss, Inc.