Abstract
PurposeModification 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.MethodsWe 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.ResultsAlmost 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.ConclusionMuc5b 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.
Highlights
Mucus gels are an essential defensive barrier on most secretory epithelia
Ten days of benzalkonium chloride (BAK) in one eye followed by 4 days without any treatment induced a −18.3% decrease in conjunctival goblet cell density
Muc5b is a biological marker of Dry eye syndrome (DES) mouse models
Summary
Mucus gels are an essential defensive barrier on most secretory epithelia. The major functions of mucus gels include lubrication and hydration of epithelial tissues. Preclinical Muc5b-GFP mouse model are mainly driven by their gel-forming mucin content. Gel-forming mucins are large heavily O-glycosylated macromolecules produced by specialized secretory cells before being excreted as multimers into the lumen to form mucus gel when in contact with water. The five genes MUC2, MUC5AC, MUC5B, MUC6, and MUC19 encoding the five gel-forming mucins in humans are conserved in mice [1,2] and are designated Muc, Muc5ac, Muc5b, Muc, and Muc. Gel-forming mucin production is regulated at two main levels: at the gene expression level (gene regulation) and by cell differentiation from undifferentiated cells into mucous cells. Abnormal or dysregulation of gel-forming mucin expression and abnormal mucous cell density are hallmarks of many mucosal diseases and mucosal damage
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