Expression of a human alpha-1,3/4-fucosyltransferase in the pit cell lineage of FVB/N mouse stomach results in production of Leb-containing glycoconjugates: a potential transgenic mouse model for studying Helicobacter pylori infection.
Helicobacter pylori is a human pathogen associated with the development of gastric and duodenal ulcers and gastric adenocarcinoma. To test the hypothesis that the human Lewis(b) blood group antigen (Le(b)) functions as a receptor for the bacteria's adhesins and mediates its attachment to gastric pit and surface mucous cells, a human alpha-1,3/4-fucosyltransferase was expressed in these cell lineages in FVB/N transgenic mice. The fucosyltransferase directed production of the Leb epitope without any apparent effect on the proliferation and differentiation programs of this lineage. Moreover, clinical isolates of H. pylori bound to these cells in transgenic mice but not in their normal littermates. Binding was blocked by pretreatment of the bacteria with soluble Le(b). This mouse model could be useful for examining the molecular pathogenesis of diseases caused by H. pylori infection. Creating novel pathways for production of specific oligosaccharides in selected cell lineages of transgenic animals represents an approach for examining the role of complex carbohydrates in regulating cellular differentiation and host-microbe interactions.
Falk
P G
PG
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
Bry
L
L
Holgersson
J
J
Gordon
J I
JI
D000818:Animals; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D005647:Fucosyltransferases / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D006001:Glycoconjugates / Q000378:metabolism; D016481:Helicobacter Infections / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007983:Lewis Blood Group Antigens; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D014018:Tissue Distribution
D006001:Glycoconjugates; D007983:Lewis Blood Group Antigens; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase