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Glycobiology Advance Access originally published online on November 8, 2008
Glycobiology 2009 19(2):182-191; doi:10.1093/glycob/cwn125
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Novel Leb-like Helicobacter pylori-binding glycosphingolipid created by the expression of human {alpha}-1,3/4-fucosyltransferase in FVB/N mouse stomach

David Fagerberg3, Jonas Ångström3, Adnan Halim3, Anna Hultberg4,2, Lena Rakhimova5, Lennart Hammarström4, Thomas Borén5 and Susann Teneberg1,3

3 Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, PO Box 440, University of Gothenburg, S-405 30 Göteborg, Sweden
4 Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital, SE 141 86 Huddinge, Stockholm, Sweden
5 Department of Medical Biochemistry and Biophysics, Umeå University, SE 901 87 Umeå, Sweden


1 To whom correspondence should be addressed: Tel: +46-31-786-34-92; Fax: +46-31-413-190; e-mail: Susann.Teneberg{at}medkem.gu.se

Received on July 15, 2008; revised on November 3, 2008; accepted on November 3, 2008

The "Leb mouse" was established as a model for investigations of the molecular events following Leb-mediated adhesion of Helicobacter pylori to the gastric epithelium. By the expression of a human {alpha}-1,3/4-fucosyltransferase in the gastric pit cell lineage of FVB/N transgenic mice, a production of Leb glycoproteins in gastric pit and surface mucous cells was obtained in this "Leb mouse," as demonstrated by binding of monoclonal anti-Leb antibodies. To explore the effects of the human {alpha}-1,3/4-fucosyltransferase on glycosphingolipid structures, neutral glycosphingolipids were isolated from stomachs of transgenic {alpha}-1,3/4-fucosyltransferase-expressing mice. A glycosphingolipid recognized by BabA-expressing H. pylori was isolated and characterized by mass spectrometry and proton NMR as Fuc{alpha}2Galβ3(Fuc{alpha}4)GalNAcβ4Galβ4Glcβ1Cer, i.e., a novel Leb-like glycosphingolipid on a ganglio core. In addition, two other novel glycosphingolipids were isolated from the mouse stomach epithelium that were found to be nonbinding with regard to H. pylori. The first was a pentaglycosylceramide, GalNAcβ3Gal{alpha}3(Fuc{alpha}2)Galβ4Glcβ1Cer, in which the isoglobo tetrasaccharide has been combined with Fuc{alpha}2 to yield an isoglobotetraosylceramide with an internal blood group B determinant. The second one was an elongated fucosyl-gangliotetraosylceramide, GalNAcβ3(Fuc{alpha}2)Galβ3GalNAcβ4Galβ4Glcβ1Cer.

Key words: transgenic Leb mouse / {alpha}-1,3 / 4-fucosyltransferase / H. pylori-binding glycosphingolipid / glycosphingolipid characterization / novel glycosphingolipid


2 Present address: Cellular Architecture and Dynamics (CA&D), Utrecht University, The Netherlands.


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A. Magalhaes, J. Gomes, M. N. Ismail, S. M Haslam, N. Mendes, H. Osorio, L. David, J. Le Pendu, R. Haas, A. Dell, et al.
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