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

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Malmberg, Emily,1978Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology (author)

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

Article/chapterEnglish2006

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American Physiological Society,2006

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LIBRIS-ID:oai:gup.ub.gu.se/61489
https://gup.ub.gu.se/publication/61489URI
https://doi.org/10.1152/ajpgi.00491.2005DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-79797URI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Gastroenterologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Gastroenterology and Hepatology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
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
Muc2; proteomics; CFTR

Added entries (persons, corporate bodies, meetings, titles ...)

Noaksson, KarinGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology (author)
Phillipson, MiaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)mjo07958 (author)
Johansson, Malin E V,1971Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xjomal (author)
Hinojosa-Kurtzberg, Marina (author)
Holm, LenaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)pho23887 (author)
Gendler, Sandra J. (author)
Hansson, Gunnar C.,1951Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xhagun (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (creator_code:org_t)

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In:American journal of physiology. Gastrointestinal and liver physiology: American Physiological Society291:20193-18571522-1547

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