title: Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: LIRIC UMR 995, Univ. Lille, Inserm, CHU Lille, Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Portal
authors.affiliation: LIRIC UMR 995, Univ. Lille, Inserm, CHU Lille, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gouyer
authors.affiliation: LIRIC UMR 995, Univ. Lille, Inserm, CHU Lille, Lille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gottrand
authors.affiliation: LIRIC UMR 995, Univ. Lille, Inserm, CHU Lille, Lille, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Desseyn
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds; D002452:Cell Count; D003228:Conjunctiva / Q000378:metabolism*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000235:genetics / Q000494:pharmacology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D055257:Mucin-5B / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001548:Benzalkonium Compounds; D018793:Interleukin-13; C524579:Muc5b protein, mouse; D055257:Mucin-5B; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins