Core 3-derived O-glycans are essential for intestinal mucus barrier function.

O-Glycans are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Core 3-derived O-glycans, which are one of the major types of O-glycans, are primarily expressed in 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 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. These data reveal a requirement for core 3-derived O-glycans in colon mucus barrier function.