To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Loss of intestinal core 1… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

Contact form








 


Note! If you want an answer on a question you must specify your email address




Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice.

Journal article
Authors Jianxin Fu
Bo Wei
Tao Wen
Malin E V Johansson
Xiaowei Liu
Emily Bradford
Kristina A Thomsson
Samuel McGee
Lilah Mansour
Maomeng Tong
J Michael McDaniel
Thomas J Sferra
Jerrold R Turner
Hong Chen
Gunnar C. Hansson
Jonathan Braun
Lijun Xia
Published in The Journal of clinical investigation
Volume 121
Issue 4
Pages 1657-66
ISSN 1558-8238
Publication year 2011
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 1657-66
Language en
Links dx.doi.org/10.1172/JCI45538
Subject categories Chemistry, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Abstract

Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that mice with intestinal epithelial cell-specific deficiency of core 1-derived O-glycans, the predominant form of O-glycans, developed spontaneous colitis that resembled human UC, including massive myeloid infiltrates and crypt abscesses. The colitis manifested in these mice was also characterized by TNF-producing myeloid infiltrates in colon mucosa in the absence of lymphocytes, supporting an essential role for myeloid cells in colitis initiation. Furthermore, induced deletion of intestinal core 1-derived O-glycans caused spontaneous colitis in adult mice. These data indicate a causal role for the loss of core 1-derived O-glycans in colitis. Finally, we detected a biosynthetic intermediate typically exposed in the absence of core 1 O-glycan, Tn antigen, in the colon epithelium of a subset of UC patients. Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase-specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia. These data suggest what we believe to be a new molecular mechanism for the pathogenesis of UC.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?