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Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments

PURPOSE: Modification of mucous cell density and gel-forming mucin production are established hallmarks of mucosal diseases. Our aim was to develop and validate a mouse model to study live goblet cell density in pathological situations and under pharmacological treatments. METHODS: We created a repo...

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Autores principales: Portal, Céline, Gouyer, Valérie, Gottrand, Frédéric, Desseyn, Jean-Luc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371386/
https://www.ncbi.nlm.nih.gov/pubmed/28355261
http://dx.doi.org/10.1371/journal.pone.0174764
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author Portal, Céline
Gouyer, Valérie
Gottrand, Frédéric
Desseyn, Jean-Luc
author_facet Portal, Céline
Gouyer, Valérie
Gottrand, Frédéric
Desseyn, Jean-Luc
author_sort Portal, Céline
collection PubMed
description PURPOSE: Modification of mucous cell density and gel-forming mucin production are established hallmarks of mucosal diseases. Our aim was to develop and validate a mouse model to study live goblet cell density in pathological situations and under pharmacological treatments. METHODS: We created a reporter mouse for the gel-forming mucin gene Muc5b. Muc5b-positive goblet cells were studied in the eye conjunctiva by immunohistochemistry and probe-based confocal laser endomicroscopy (pCLE) in living mice. Dry eye syndrome (DES) model was induced by topical application of benzalkonium chloride (BAK) and recombinant interleukine (rIL) 13 was administered to reverse the goblet cell loss in the DES model. RESULTS: Almost 50% of the total of conjunctival goblet cells are Muc5b(+) in unchallenged mice. The decrease density of Muc5b(+) conjunctival goblet cell population in the DES model reflects the whole conjunctival goblet cell loss. Ten days of BAK in one eye followed by 4 days without any treatment induced a −18.3% decrease in conjunctival goblet cell density. A four days of rIL13 application in the DES model restored the normal goblet cell density. CONCLUSION: Muc5b is a biological marker of DES mouse models. We bring the proof of concept that our model is unique and allows a better understanding of the mechanisms that regulate gel-forming mucin production/secretion and mucous cell differentiation in the conjunctiva of living mice and can be used to test treatment compounds in mucosal disease models.
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spelling pubmed-53713862017-04-07 Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments Portal, Céline Gouyer, Valérie Gottrand, Frédéric Desseyn, Jean-Luc PLoS One Research Article PURPOSE: Modification of mucous cell density and gel-forming mucin production are established hallmarks of mucosal diseases. Our aim was to develop and validate a mouse model to study live goblet cell density in pathological situations and under pharmacological treatments. METHODS: We created a reporter mouse for the gel-forming mucin gene Muc5b. Muc5b-positive goblet cells were studied in the eye conjunctiva by immunohistochemistry and probe-based confocal laser endomicroscopy (pCLE) in living mice. Dry eye syndrome (DES) model was induced by topical application of benzalkonium chloride (BAK) and recombinant interleukine (rIL) 13 was administered to reverse the goblet cell loss in the DES model. RESULTS: Almost 50% of the total of conjunctival goblet cells are Muc5b(+) in unchallenged mice. The decrease density of Muc5b(+) conjunctival goblet cell population in the DES model reflects the whole conjunctival goblet cell loss. Ten days of BAK in one eye followed by 4 days without any treatment induced a −18.3% decrease in conjunctival goblet cell density. A four days of rIL13 application in the DES model restored the normal goblet cell density. CONCLUSION: Muc5b is a biological marker of DES mouse models. We bring the proof of concept that our model is unique and allows a better understanding of the mechanisms that regulate gel-forming mucin production/secretion and mucous cell differentiation in the conjunctiva of living mice and can be used to test treatment compounds in mucosal disease models. Public Library of Science 2017-03-29 /pmc/articles/PMC5371386/ /pubmed/28355261 http://dx.doi.org/10.1371/journal.pone.0174764 Text en © 2017 Portal et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Portal, Céline
Gouyer, Valérie
Gottrand, Frédéric
Desseyn, Jean-Luc
Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments
title Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments
title_full Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments
title_fullStr Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments
title_full_unstemmed Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments
title_short Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments
title_sort preclinical mouse model to monitor live muc5b-producing conjunctival goblet cell density under pharmacological treatments
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371386/
https://www.ncbi.nlm.nih.gov/pubmed/28355261
http://dx.doi.org/10.1371/journal.pone.0174764
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