Abnormal expression of Muc5b in Cftr-null mice and in mammary tumors of MMTV-ras mice
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Gel-forming mucins are large, high molecular weight, and heavily O-glycosylated proteins that are responsible for the rheological properties of mucus gel. Among them, the mucin MUC5B has been implicated in breast cancer and cystic fibrosis. We obtained a new polyclonal serum, named CP1, which was isolated from a rabbit immunized with a mouse Muc5b peptide. The immunoprofile of Muc5b was determined on paraffin-embedded and frozen mouse tissue sections and showed a similar expression pattern in mouse to that in the human. The “nonmammary” mucin Muc5b was detected in all mammary tumors analyzed from MMTV-ras mice, suggesting that the CP1 antibody is a valuable tool for investigating the involvement of this mucin in mammary cancer. We also found that uninfected Cftr −/− mice harbored more Clara cells, which were Muc5b-positive, than did their wild-type control littermates. The number of Muc5b-positive cells increased in Cftr −/− mice infected experimentally with Pseudomonas aeruginosa, and the mice developed mucus plugs in their bronchi and bronchioles with a high frequency of Muc5b content (87%, Cohen’s kappa = 0.82; p < 0.0001). These findings suggest that mice genetically deficient in the Cftr gene are predisposed to develop mucus plugs and that MUC5B may provide a valuable target for decreasing mucus viscosity in cystic fibrosis.
KeywordsGel-forming mucin Muc5b Breast cancer Cystic fibrosis Mucus plug
We thank the microbiology department of the Centre de Biologie-Pathologie Pierre-Marie Degand (Lille Hospital) for access to the ABI Prism 7700; MH Gevaert and RM Siminski (Service Commun-Morphologie cellulaire, Université Lille 2) for slides; J Bara (Inserm UMR S938, Paris, France) for the 45M1 antibody; J Ryerse (Department of Pathology, Saint Louis, MO) for the anti-CCSP (R42AP) antibody; and MR Parsek and BR Borlee (Seattle, WA) for the PAO1 strain. This study was supported by the French Cystic Fibrosis Association Vaincre la Mucoviscidose (JLD, FC0203, and IC0806).
- Bartlett NW, Walton RP, Edwards MR, Aniscenko J, Caramori G, Zhu J, Glanville N, Choy KJ, Jourdan P, Burnet J, Tuthill TJ, Pedrick MS, Hurle MJ, Plumpton C, Sharp NA, Bussell JN, Swallow DM, Schwarze J, Guy B, Almond JW, Jeffery PK, Lloyd CM, Papi A, Killington RA, Rowlands DJ, Blair ED, Clarke NJ, Johnston SL (2008) Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat Med 14:199–204PubMedCrossRefGoogle Scholar
- Desseyn JL, Gouyer V, Tetaert D (2008) Architecture of the gel-forming mucins. In: Van Seuningen I (ed) The epithelial mucins: structure/function. Roles in cancer and inflammatory diseases. Signpost, KeralaGoogle Scholar
- Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, Evans CM, Garantziotis S, Adler KB, Dickey BF, du Bois RM, Yang IV, Herron A, Kervitsky D, Talbert JL, Markin C, Park J, Crews AL, Slifer SH, Auerbach S, Roy MG, Lin J, Hennessy CE, Schwarz MI, Schwartz DA (2011) A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 364:1503–1512PubMedCrossRefGoogle Scholar