Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies using sulfotransferase-deficient mice have revealed various physiological functions of sulfated glycans. Studies using gene-targeted mice deficient in both N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2 showed that these sulfotransferases play critical roles in lymphocyte homing. Recent studies indicated that GlcNAc6ST-2 is expressed not only in lymph node high endothelial venules but also in the colonic epithelial cells in mice, and that this sulfotransferase plays a critical role in GlcNAc-6-O-sulfation of the colonic-mucins, as revealed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry of the colonic-mucin O-glycans from wild-type (WT) and GlcNAc6ST-2-deficient mice. After induction of colitis by dextran sulfate sodium, significantly more leukocyte infiltration was observed in the colon of GlcNAc6ST-2-deficient mice than in that of WT mice. These studies demonstrate that GlcNAc-6-O-sulfotransferases play important roles not only in lymphoid tissues but also in nonlymphoid tissues. This chapter describes experimental procedures for assessing the functions of GlcNAc-6-O-sulfotransferases using gene-targeted mice.
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PMID:Roles of GlcNAc-6-O-sulfotransferases in lymphoid and nonlymphoid tissues. 2081 70

MUC2 is the major gel-forming colonic mucin that forms the two mucus layers. Recent studies using gene-targeted mice have revealed the physiological functions of Muc2, the mouse counterpart of human MUC2, and its O-glycosylation in the colon. Muc2-deficient mice spontaneously developed colitis and colorectal cancer. As for the O-glycosylation of Muc2, conditional core 1-derived O-glycan-deficient mice in the intestines exhibited a breached inner mucus layer and spontaneously developed colitis. Similarly, core 3-derived O-glycan-deficient mice exhibited an increased susceptibility to colitis and colorectal cancer, suggesting that both core 1- and core 3-derived O-glycans on Muc2 are required for colonic protection. Mice deficient in core 2-branched O-glycans synthesized after the formation of core 1 O-glycans also exhibited increased experimental colitis. Furthermore, our recent studies using gene-targeted mice deficient in N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-2 revealed that sulfation of the core 2-branched O-glycans of the colonic mucins by GlcNAc6ST-2 is required for the protection against experimental colitis. Taken together, these findings demonstrate the critical roles of the MUC2 mucin and its various O-glycans in the protection against colitis and colorectal cancer. Consistently, various alterations in the expression of mucins and their O-glycosylation have been noted in clinical samples of colorectal cancer. This review focuses on the roles of the MUC2 core protein and its O-glycosylation in health and disease.
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PMID:Roles of the gel-forming MUC2 mucin and its O-glycosylation in the protection against colitis and colorectal cancer. 2303 53