Abnormal expression of Muc5b in Cftr-null mice and in mammary tumors of MMTV-ras mice |
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Authors: | Hélène Valque Valérie Gouyer Marie-Odile Husson Frédéric Gottrand Jean-Luc Desseyn |
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Institution: | 1.Inserm U995, Faculté de Médecine, P?le Recherche, Bat. Huriez, 5ème étage,University Lille 2,Lille,France;2.CHRU of Lille,Lille,France |
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Abstract: | 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. |
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