Detailed O-glycomics of the Muc2 mucin from colon of wild-type, core 1-and core 3-transferase-deficient mice highlights differences compared with human MUC2

作者：Thomsson Kristina A^*; Holmen Larsson Jessica M; Angstrom Jonas; Johansson Malin E V; Xia Lijun; Hansson Gunnar C

来源：Glycobiology, 2012, 22(8): 1128-1139.

DOI：10.1093/glycob/cws083

• LC
• mass spectrometry
• mucin
• murine
• O-glycosylation

The heavily O-glycosylated mucin MUC2 constitutes the major protein in the mucosal layer that acts as a physical barrier protecting the epithelial layer in the colon. In this study, Muc2 was purified from mucosal scrapings from the colon of wild-type (WT) mice, core 3 transferase knockout (C3Gnt(-/-)) mice and intestinal epithelial cell-specific core 1 knockout (IEC C1Galt1(-/-)) mice. The Muc2 O-glycans were released by reductive beta-elimination and analyzed with liquid chromatography-mass spectrometry in the negative-ion mode. Muc2 from the distal colon of WT and C3Gnt(-/-) knockout mice carried a mixture of core 1- or core 2-type glycans, whereas Muc2 from IEC C1Galt1(-/-) mice carried highly sialylated core 3- and core 4-type glycans. A large portion of NeuAc in all mouse models was positioned on disialylated N-acetyllactosamine units, an epitope not reported on human colonic MUC2. Mass spectra and proton NMR spectroscopy revealed an abundant NeuAc linked to internally positioned N-acetylglucosamine on colonic murine Muc2, which also differs markedly from human MUC2. Our results highlight that murine colonic Muc2 O-glycosylation is substantially different from human MUC2, which could be one explanation for the different commensal microbiota of these two species.

• 出版日期2012-8