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Increased levels of mucins in the cystic fibrosis mouse small intestine, and modulator effects of the Muc1 mucin expression.

Journal article
Authors Emily Malmberg
Karin Noaksson
Mia Phillipson
Malin E V Johansson
Marina Hinojosa-Kurtzberg
Lena Holm
Sandra J. Gendler
Gunnar C. Hansson
Published in American journal of physiology. Gastrointestinal and liver physiology
Volume 291
Issue 2
Pages G203-10
ISSN 0193-1857
Publication year 2006
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages G203-10
Language en
Links dx.doi.org/10.1152/ajpgi.00491.2005
Keywords Animals, CA-15-3 Antigen, analysis, chemistry, metabolism, Cystic Fibrosis, metabolism, Intestine, Small, metabolism, Mice, Mice, Inbred C57BL, Mice, Inbred CFTR, Mucins, metabolism, Solubility, Up-Regulation
Subject categories Medical and Health Sciences

Abstract

The mouse model (Cftr(tm1UNC)/Cftr(tm1UNC)) for cystic fibrosis (CF) shows mucus accumulation and increased Muc1 mucin mRNA levels due to altered splicing (Hinojosa-Kurtzberg AM, Johansson MEV, Madsen CS, Hansson GC, and Gendler SJ. Am J Physiol Gastrointest Liver Physiol 284: G853-G862, 2003). However, it is not known whether Muc1 is a major mucin contributing to the increased mucus and why CF/Muc1-/- mice show lower mucus accumulation. To address this, we have purified mucins from the small intestine of CF mice using guanidinium chloride extraction, ultracentrifugation, and gel filtration and analyzed them by slot blot, gel electrophoresis, proteomics, and immunoblotting. Normal and CF mice with wild-type (WT) Muc1 or Muc1-/- or that are transgenic for human MUC1 (MUC1.Tg, on a Muc1-/- background) were analyzed. The total amount of mucins, both soluble and insoluble in guanidinium chloride, increased up to 10-fold in the CF mice compared with non-CF animals, whereas the CF mice lacking Muc1 showed intermediate levels between the CF and non-CF mice. However, the levels of Muc3 (orthologue of human MUC17) were increased in the CF/Muc1-/- mice compared with the CF/MUC1.Tg animals. The amount of MUC1 mucin was increased several magnitudes in the CF mice, but MUC1 did still not appear to be a major mucin. The amount of insoluble mucus of the large intestine was also increased in the CF mice, an effect that was partially restored in the CF/Muc1-/- mice. The thickness of the firmly adherent mucus layer of colon in the Muc1-/- mice was significantly lower than that of WT mice. The results suggest that MUC1 is not a major component in the accumulated mucus of CF mice and that MUC1 can influence the amount of other mucins in a still unknown way.

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