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

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 p...

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Bibliographic Details
Published in:The Journal of experimental medicine 2007-06, Vol.204 (6), p.1417-1429
Main Authors: An, Guangyu, Wei, Bo, Xia, Baoyun, McDaniel, J Michael, Ju, Tongzhong, Cummings, Richard D, Braun, Jonathan, Xia, Lijun
Format: Article
Language:English
Subjects:
Animals
Colitis - metabolism
Colitis - pathology
Colon - ultrastructure
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Disease Susceptibility - metabolism
DNA Primers
Immunoblotting
Immunohistochemistry
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Mucin-2
Mucins - metabolism
N-Acetylglucosaminyltransferases - deficiency
N-Acetylglucosaminyltransferases - genetics
Polysaccharides - metabolism
Reverse Transcriptase Polymerase Chain Reaction
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Summary: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.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20061929