Background: A subtraction screen isolated CRP-ductin (CRP), a gene expressed in intestinal crypts.
Methods: DNA sequencing, in situ hybridization, immunostaining, Western and Northern blotting were used to characterize murine CRP.
Results: CRP is restricted to the intestine and its associated glands. In the small intestine, CRP mRNA is expressed in crypt cells at all stages of differentiation from the stem cells to the terminally differentiating cells of the crypt top, but not in the mature cells of the villus. In the colon, CRP mRNA is most heavily expressed in the mid-crypt. Expression is also seen in the pancreas and pancreatic ducts, and in the epithelium lining larger hepatic ducts, but not in the liver parenchyma or stomach. CRP protein is localized to the 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 cells lining the pancreatic duct system and the larger hepatic ducts. Two cDNA variants, CRP-alpha and CRP-beta, were cloned from mouse jejunal 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 extracellular region composed of many repeats (8 scavenger receptor domains, 5 CUB-domains, 1 ZP-domain, and 6 copies of a previously unreported domain which we call the CRP-domain). The structure of the CRP protein suggests a role in ligand interaction; possible functions are discussed.