Increased susceptibility to colitis and colorectal tumors in mice lacking core 3–derived O-glycans (original) (raw)
Article| May 21 2007
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
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4Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
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5Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322
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1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
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5Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322
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5Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322
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4Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
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1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
2Department of Biochemistry and Molecular Biology,
3Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
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Guangyu An
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Bo Wei
4Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
Baoyun Xia
5Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322
J. Michael McDaniel
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
Tongzhong Ju
5Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322
Richard D. Cummings
5Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322
Jonathan Braun
4Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
Lijun Xia
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
2Department of Biochemistry and Molecular Biology,
3Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Abbreviations used: AOM, azoxymethane; C3GnT, core 3 β1,3-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.
Received: September 07 2006
Accepted: April 26 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (6): 1417–1429.
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 β1,3-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.
The Rockefeller University Press
2007
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