Muc5b-deficient mice develop early histological lung abnormalities
| Autor: | Marc Le Bert, Christophe Leboeuf, Frédéric Gottrand, Anne Janin, Philippe Marquillies, Catherine Duez, Jean-Luc Desseyn, Valérie Gouyer, Hélène Valque, Ségolène Plet, Bernhard Ryffel |
|---|---|
| Přispěvatelé: | Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), This study (J.-L.D.) was supported in part by the French Cystic Fibrosis Association – Vaincre la Mucoviscidose and by the SFR Maladies Infectieuses, Inflammatoires Immunitaires – FED 4258. H.V. was the recipient of a fellowship from the University of Lille/Ministry of Higher Education and Research., We thank M. Holzenberger (Inserm UMRS 938, Paris, France) for the MeuCre40 mouse strain, M. Tauc (CNRS FRE 3093, Nice, France) for the CCSP-Cre mouse strain, C. Goujet-Zalc (CNRS, SEAT UPS44, Villejuif, France) for the generation of Tg mice, J. S. Ryerse (Dept. of Pathology, St Louis University, MO, USA) for the anti-CCSP antibody, M. H. Gevaert and R. M. Siminski (Service Commun-Morphologie Cellulaire, University of Lille, France) for slides, J. Devassine and R. Dehaynin from the EOPS animal facility (University of Lille, France) for mouse colony management and P. Roussel for critical reading of the manuscript and useful discussions., Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Inserm, CHU Lille, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Lille Inflammation Research International Center - U 995 [LIRIC], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Lille Inflammation Research International Center (LIRIC) - U995 |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Pathology
medicine.medical_specialty QH301-705.5 Science Knockout [SDV]Life Sciences [q-bio] Biology Pulmonary function testing 03 medical and health sciences 0302 clinical medicine Immune system Gel-forming mucin In vivo Metaplasia medicine Biology (General) 030304 developmental biology 0303 health sciences Lung Mucin Respiratory distress respiratory system Mucus 3. Good health Young mice medicine.anatomical_structure 030228 respiratory system biology.protein medicine.symptom Elastin Research Article |
| Zdroj: | Biology Open Biology Open, Royal Society, 2019, 8, pp.bio046359. ⟨10.1242/bio.046359⟩ Biology Open, Vol 8, Iss 11 (2019) Biology Open, 2019, 8, pp.bio046359. ⟨10.1242/bio.046359⟩ |
| ISSN: | 2046-6390 |
| DOI: | 10.1242/bio.046359⟩ |
| Popis: | Gel-forming mucins are the main organic component responsible for physical properties of the mucus hydrogels. While numerous biological functions of these mucins are well documented, specific physiological functions of each mucin are largely unknown. To investigate in vivo functions of the gel-forming mucin Muc5b, which is one of the major secreted airway mucins, along with Muc5ac, we generated mice in which Muc5b was disrupted and maintained in the absence of environmental stress. Adult Muc5b-deficient mice displayed bronchial hyperplasia and metaplasia, interstitial thickening, alveolar collapse, immune cell infiltrates, fragmented and disorganized elastin fibers and collagen deposits that were, for approximately one-fifth of the mice, associated with altered pulmonary function leading to respiratory failure. These lung abnormalities start early in life, as demonstrated in one-quarter of 2-day-old Muc5b-deficient pups. Thus, the mouse mucin Muc5b is essential for maintaining normal lung function. Summary: The gelling mucin MUC5B is essential for the mucociliary clearance at adulthood. Here we show that Muc5b-deficient mice exhibit an early lung inflammation that may lead to respiratory distress. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|