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

Methods Enzymol. 2010:479:123-41. doi: 10.1016/S0076-6879(10)79007-8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Galactosyltransferases / genetics
  • Galactosyltransferases / metabolism
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism*
  • Mice
  • Mice, Knockout
  • Mucus / chemistry*
  • Mucus / metabolism*
  • Polysaccharides / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Polysaccharides
  • Galactosyltransferases