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 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.
An
Guangyu
G
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Wei
Bo
B
Xia
Baoyun
B
McDaniel
J Michael
JM
Ju
Tongzhong
T
Cummings
Richard D
RD
Braun
Jonathan
J
Xia
Lijun
L
D000818:Animals; D003092:Colitis / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000648:ultrastructure; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D004198:Disease Susceptibility / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics; D011134:Polysaccharides / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases