The Journal of Experimental Medicine
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Published online May 21, 2007
doi:10.1084/jem.20061929
The Journal of Experimental Medicine, Vol. 204, No. 6, 1417-1429
The Rockefeller University Press, 0022-1007 $30.00
© 2007 An et al.
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ARTICLE

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

Guangyu An1, Bo Wei4, Baoyun Xia5, J. Michael McDaniel1, Tongzhong Ju5, Richard D. Cummings5, Jonathan Braun4, and Lijun Xia1,2,3

1 Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 2 Department of Biochemistry and Molecular Biology, and 3 Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
4 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
5 Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322

CORRESPONDENCE Lijun Xia: lijun-xia{at}omrf.ouhsc.edu

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 ß1,3-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.

Abbreviations used: AOM, azoxymethane; C3GnT, core 3 ß1,3-N-acetylglucosaminyltransferase; DSS, dextran sodium sulfate; HRP, horseradish peroxidase; IBD, inflammatory bowel disease; IEL, intraepithelial lymphocyte; ITF, intestinal trefoil factor; LPL, lamina propria lymphocyte; O-glycans, O-linked oligosaccharides; PAS, periodic acid-Schiff's reagent.


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