Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans.

An G, Wei B, Xia B, McDaniel JM, Ju T, Cummings RD, Braun J, Xia L
J Exp Med. 2007 204 (6): 1417-29

PMID: 17517967 · PMCID: PMC2118614 · DOI:10.1084/jem.20061929

Altered intestinal O-glycan expression has been observed in patients with ulcerative colitis and colorectal cancer, but the role of this alteration in the etiology of these diseases is unknown. O-glycans in mucin core proteins are the predominant components of the intestinal mucus, which comprises part of the intestinal mucosal barrier. Core 3-derived O-glycans, which are one of the major types of O-glycans, are primarily expressed in the colon. To investigate the biological function of core 3-derived O-glycans, we engineered mice lacking core 3 beta1,3-N-acetylglucosaminyltransferase (C3GnT), an enzyme predicted to be important in the synthesis of core 3-derived O-glycans. Disruption of the C3GnT gene eliminated core 3-derived O-glycans. C3GnT-deficient mice displayed a discrete, colon-specific reduction in Muc2 protein and increased permeability of the intestinal barrier. Moreover, these mice were highly susceptible to experimental triggers of colitis and colorectal adenocarcinoma. These data reveal a requirement for core 3-derived O-glycans in resistance to colonic disease.

MeSH Terms (16)

Animals Colitis Colon Colorectal Neoplasms Disease Susceptibility DNA Primers Immunoblotting Immunohistochemistry Mice Mice, Knockout Microscopy, Electron, Transmission Mucin-2 Mucins N-Acetylglucosaminyltransferases Polysaccharides Reverse Transcriptase Polymerase Chain Reaction

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