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Gene Review

Muc2  -  mucin 2

Mus musculus

Synonyms: 2010015E03Rik, Colonic mucin, MCM, MUC-2, Mucin-2, ...
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Disease relevance of Muc2


High impact information on Muc2

  • Analyses of the mucins Muc2, Muc3, and Muc5ac showed lower levels of RNA expression in the CF mice and similar levels of protein [6].
  • Colonic goblet cells in the Muc2(-/-) mice were negative for Muc2, but trefoil factor 3 was still detectable [7].
  • Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection [7].
  • There was also decreased goblet cell differentiation as assessed by alcian blue staining and expression of the Muc2 gene, especially in mice fed the Western-style diet, although this differentiation lineage was still present as indicated by expression and staining for intestinal trefoil factor [8].
  • However, Klf4(-/-) mice demonstrate a 90% decrease in the number of goblet cells in the colon, show abnormal expression of the goblet cell-specific marker Muc2 by in situ hybridization, have abnormal staining of the colonic epithelium with Alcian Blue for acidic mucins, and lack normal goblet cell morphology by ultrastructural analysis [9].

Chemical compound and disease context of Muc2


Biological context of Muc2

  • This gene is clustered with the three secreted large gel-forming mucins Muc2, Muc5ac, and Muc5b in a region that exhibits synteny with human chromosome 11p15 [10].
  • RESULTS: Antibiotic treatment did not significantly affect Muc2 and Muc3 gene expression in CF mice [11].
  • The murine Muc2 mucin gene is transcriptionally regulated by the zinc-finger GATA-4 transcription factor in intestinal cells [12].
  • Four GATA-4 cis-elements were identified in the promoter by EMSA and Muc2 promoter was efficiently activated when GATA-4 was overexpressed in the cells with a loss of transactivation when those sites were either mutated or a mutated form of GATA-4 was used [12].
  • Having found putative GATA binding sites in the murine Muc2 promoter and that GATA-4 is expressed in Muc2-expressing goblet cells of the mouse small intestine, we undertook to study its regulation by this transcription factor [12].

Anatomical context of Muc2

  • Muc2(-/-) mice develop tumors in the small and large intestine and the rectum, but in contrast to tumors in Apc1638(+/-) mice, this does not involve increased expression or nuclear localization of beta-catenin [1].
  • A possible explanation is the mechanism by which Muc2 deficiency may trigger the immune system to release interleukin-10, an anti-inflammatory cytokine before MTX-treatment [4].
  • These quantitative and structural aberrations in Muc2 in IL-10 mice likely reduce the ability of their mucosa to cope with nonpathogenic commensal bacteria and may contribute to their susceptibility to develop colitis [13].
  • To help us investigate the role of mucin in the protection of the colonic epithelium in the mouse, we aimed to identify the murine colonic mucin (MCM) and its encoding gene [14].
  • We isolated MCM, raised an anti-MCM antiserum, and studied the biosynthesis of MCM in the gastrointestinal tract [14].

Associations of Muc2 with chemical compounds

  • To independently identify murine Muc2, we cloned a cDNA fragment from murine colonic mRNA, encoding the 302 NH2-terminal amino acids of murine Muc2 [14].
  • Prior to MTX-injection, tumor necrosis factor-alpha and interleukin-10 mRNAs were upregulated in Muc2(-/-) mice, probably due to continuous exposure of the intestine to luminal antigens [4].
  • The mucin Muc2, which is a major determinant of goblet cell morphology, was expressed in most goblet cells, yet only in cells staining positive for both Alcian blue and high iron diamine [15].
  • Muc2 in distal IL10-/- colon contained significantly less sulfate residues than in controls, which may compromise its protective properties [15].
  • MCM levels were decreased 4-fold at 7 days of allergen exposure in -/- mice and at 15 days in +/+ mice [16].

Physical interactions of Muc2

  • Two discrete types of mucin proteins exist in the mouse intestine, secretory Muc2 and membrane-bound Muc3 [17].

Regulatory relationships of Muc2

  • Inactivation of p21WAF1/cip1 enhances intestinal tumor formation in Muc2-/- mice [1].

Other interactions of Muc2


Analytical, diagnostic and therapeutic context of Muc2


  1. Inactivation of p21WAF1/cip1 enhances intestinal tumor formation in Muc2-/- mice. Yang, W., Velcich, A., Lozonschi, I., Liang, J., Nicholas, C., Zhuang, M., Bancroft, L., Augenlicht, L.H. Am. J. Pathol. (2005) [Pubmed]
  2. MUC genes are differently expressed during onset and maintenance of inflammation in dextran sodium sulfate-treated mice. Hoebler, C., Gaudier, E., De Coppet, P., Rival, M., Cherbut, C. Dig. Dis. Sci. (2006) [Pubmed]
  3. Colorectal cancer in mice genetically deficient in the mucin Muc2. Velcich, A., Yang, W., Heyer, J., Fragale, A., Nicholas, C., Viani, S., Kucherlapati, R., Lipkin, M., Yang, K., Augenlicht, L. Science (2002) [Pubmed]
  4. Methotrexate-induced mucositis in mucin 2-deficient mice. de Koning, B.A., Sluis, M., Lindenbergh-Kortleve, D.J., Velcich, A., Pieters, R., B??ller, H.A., Einerhand, A.W., Renes, I.B. J. Cell. Physiol. (2007) [Pubmed]
  5. IFN-gamma, but not Fas, mediates reduction of allergen-induced mucous cell metaplasia by inducing apoptosis. Shi, Z.O., Fischer, M.J., De Sanctis, G.T., Schuyler, M.R., Tesfaigzi, Y. J. Immunol. (2002) [Pubmed]
  6. Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus. Parmley, R.R., Gendler, S.J. J. Clin. Invest. (1998) [Pubmed]
  7. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Van der Sluis, M., De Koning, B.A., De Bruijn, A.C., Velcich, A., Meijerink, J.P., Van Goudoever, J.B., Büller, H.A., Dekker, J., Van Seuningen, I., Renes, I.B., Einerhand, A.W. Gastroenterology (2006) [Pubmed]
  8. Targeted inactivation of p27kip1 is sufficient for large and small intestinal tumorigenesis in the mouse, which can be augmented by a Western-style high-risk diet. Yang, W., Bancroft, L., Nicholas, C., Lozonschi, I., Augenlicht, L.H. Cancer Res. (2003) [Pubmed]
  9. The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Katz, J.P., Perreault, N., Goldstein, B.G., Lee, C.S., Labosky, P.A., Yang, V.W., Kaestner, K.H. Development (2002) [Pubmed]
  10. Characterization of mouse muc6 and evidence of conservation of the gel-forming mucin gene cluster between human and mouse. Desseyn, J.L., Laine, A. Genomics (2003) [Pubmed]
  11. Eradication of small intestinal bacterial overgrowth in the cystic fibrosis mouse reduces mucus accumulation. De Lisle, R.C., Roach, E.A., Norkina, O. J. Pediatr. Gastroenterol. Nutr. (2006) [Pubmed]
  12. The murine Muc2 mucin gene is transcriptionally regulated by the zinc-finger GATA-4 transcription factor in intestinal cells. van der Sluis, M., Melis, M.H., Jonckheere, N., Ducourouble, M.P., Büller, H.A., Renes, I., Einerhand, A.W., Van Seuningen, I. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  13. Interleukin 10-deficient mice exhibit defective colonic Muc2 synthesis before and after induction of colitis by commensal bacteria. Schwerbrock, N.M., Makkink, M.K., van der Sluis, M., Büller, H.A., Einerhand, A.W., Sartor, R.B., Dekker, J. Inflamm. Bowel Dis. (2004) [Pubmed]
  14. Gastrointestinal expression and partial cDNA cloning of murine Muc2. van Klinken, B.J., Einerhand, A.W., Duits, L.A., Makkink, M.K., Tytgat, K.M., Renes, I.B., Verburg, M., Büller, H.A., Dekker, J. Am. J. Physiol. (1999) [Pubmed]
  15. Fate of goblet cells in experimental colitis. Makkink, M.K., Schwerbrock, N.M., Mähler, M., Boshuizen, J.A., Renes, I.B., Cornberg, M., Hedrich, H.J., Einerhand, A.W., Büller, H.A., Wagner, S., Enss, M.L., Dekker, J. Dig. Dis. Sci. (2002) [Pubmed]
  16. Bax is crucial for IFN-gamma-induced resolution of allergen-induced mucus cell metaplasia. Tesfaigzi, Y., Fischer, M.J., Daheshia, M., Green, F.H., De Sanctis, G.T., Wilder, J.A. J. Immunol. (2002) [Pubmed]
  17. Coordinated Muc2 and Muc3 mucin gene expression in Trichinella spiralis infection in wild-type and cytokine-deficient mice. Shekels, L.L., Anway, R.E., Lin, J., Kennedy, M.W., Garside, P., Lawrence, C.E., Ho, S.B. Dig. Dis. Sci. (2001) [Pubmed]
  18. Targeted disruption of the murine mucin gene 1 decreases susceptibility to cholesterol gallstone formation. Wang, H.H., Afdhal, N.H., Gendler, S.J., Wang, D.Q. J. Lipid Res. (2004) [Pubmed]
  19. Temporal analysis of goblet cells and mucin gene expression in murine models of allergic asthma. Shahzeidi, S., Aujla, P.K., Nickola, T.J., Chen, Y., Alimam, M.Z., Rose, M.C. Exp. Lung Res. (2003) [Pubmed]
  20. Monocyte inflammation augments acrolein-induced Muc5ac expression in mouse lung. Borchers, M.T., Wesselkamper, S., Wert, S.E., Shapiro, S.D., Leikauf, G.D. Am. J. Physiol. (1999) [Pubmed]
  21. Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice. Eliakim, R., Fan, Q.X., Babyatsky, M.W. European journal of gastroenterology & hepatology. (2002) [Pubmed]
  22. The Sp family of transcription factors in the regulation of the human and mouse MUC2 gene promoters. Aslam, F., Palumbo, L., Augenlicht, L.H., Velcich, A. Cancer Res. (2001) [Pubmed]
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