title: Intestinal mucins from cystic fibrosis mice show increased fucosylation due to an induced Fucalpha1-2 glycosyltransferase.
abstract: In gene-targeted mouse models for cystic fibrosis (CF), the disease is mainly manifested by mucus obstruction in the intestine. To explore the mucus composition, mucins insoluble and soluble in 6 M guanidinium chloride were purified by three rounds of isopycnic ultracentrifugation from the small and large intestines of CF mice (Cftr(m1UNC)/Cftr(m1UNC)) and compared with wild-type mice. The amino acid composition was typical of that for mucins and showed increased amounts of the insoluble (2.5-fold increase) and soluble (7-fold increase) mucins in the small intestine of the CF mice compared with wild-type mice. Mucins from the large intestine of both wild-type and CF mice showed a high but constant level of fucosylation. In contrast, the insoluble and soluble mucins of the small intestine in CF mice revealed a large increase in fucose, whereas those of wild-type mice contained only small amounts of fucose. This increased fucosylation was analysed by releasing the O-linked oligosaccharides followed by GC-MS. NMR spectroscopy revealed that the increased fucosylation was due to an increased expression of blood group H epitopes (Fucalpha1-2Gal-). Northern-blot analysis, using a probe for the murine Fucalpha1-2 fucosyltransferase (Fut2), showed an up-regulation of this mRNA in the small intestine of the CF mice, suggesting that this enzyme is responsible for the observed increase in blood group H-type glycosylation. The reason for this up-regulation could be a direct or indirect effect of a non-functional CF transmembrane conductance regulator (CFTR) caused by the absence of CFTR channel.
authors.affiliation: Department of Medical Biochemistry, Göteborg University, Medicinaregatan 9A, 41390 Gothenburg, Sweden.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Thomsson
authors.forename: Marina
authors.initials: M
authors.lastname: Hinojosa-Kurtzberg
authors.forename: Karin A
authors.initials: KA
authors.lastname: Axelsson
authors.forename: Steven E
authors.initials: SE
authors.lastname: Domino
authors.forename: John B
authors.initials: JB
authors.lastname: Lowe
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Gendler
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002849:Chromatography, Gas; D003550:Cystic Fibrosis / Q000378:metabolism*; D005643:Fucose / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D009077:Mucins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D009077:Mucins; D005643:Fucose; D016695:Glycosyltransferases