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MUCOSAL BIOLOGY

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

¹Department of Medical Biochemistry, Göteborg University, Gothenburg, Sweden; ²Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; and ³Mayo Clinic College of Medicine, Scottsdale, Arizona

Submitted 18 October 2005 ; accepted in final form 20 February 2006

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.

Muc2; proteomics; CFTR

This article has been cited by other articles:

				R. C. De Lisle, E. Roach, and K. Jansson Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G577 - G584. [Abstract] [Full Text] [PDF]