CHARACTERIZATION OF MICE WITH TARGETED DELETION OF THE GENE ENCODING CORE 2 β1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE-2

The three glycosyltransferases of the Core 2 beta 1,6-N-acetylglucosaminyltransferase (C2GnT) family, C2GnT1, C2GnT2, and C2GnT3, are able to initiate the Core 2 branch of O-glycans. However, C2GnT2, which is highly expressed in the digestive tract, has a broader acceptor substrate specificity that allows it to also generate Core 4 O-glycans and I branches. We discovered that C2GnT2 KO mice have decreased mucosal barrier function in the digestive tract, reduced levels of circulating IgGs and fecal IgA, and increased susceptibility to experimental colitis. Mass spectrometric analyses also revealed that C2GnT2 KO mice had a reduction in Core 2 O-glycans in the digestive tract with a corresponding increase in elongated Core 1 O-glycans. Unexpectedly, we saw that the loss of C2GnT2 and especially the loss of all three C2GnT5 resulted in the expression of elongated O-mannose structures in the stomach, suggesting that the elongation of these structures is controlled by competition for UDP-GlcNAc [Stone, E. L., Ismail, M. N., Lee, S. H., Luu, Y., Ramirez, K., Haslam, S. M., Ho, S. B., Dell, A., Fukuda, M. and Marth, J. D. (2009). Glycosyltransferase function in Core 2-type protein O-glycosylation. Mol. Cell. Biol. 29, 337O-3782].