Alteration of ocular surface mucins in MUC5AC-DTA transgenic mice

PURPOSE To investigate the compensation of secretory mucins with membranous mucins in mice with goblet cell deficiency. METHODS A transgenic mouse model in which conjunctival goblet cells were targeted was generated, and the expression of mucins was evaluated through the toxicity of diphtheria toxin A driven by a human mucin, MUC5AC, promoter. Immunohistochemical staining, in situ hybridization, electronic microscopy, and quantitative reverse transcription polymerase chain reaction (RT-PCR) were used to characterize their phenotypes. RESULTS The external appearance of the ocular surface was normal, and no corneal pathology was found. The quantity of MUC5AC and the number of conjunctival goblet cells decreased in this mouse as expected. However, the membranous mucin, MUC4, compensates the decrease of MUC5AC in terms of the results of immunohistochemical staining, in situ hybridization, electronic microscopy, and quantitative RT-PCR. CONCLUSIONS The membranous mucin, MUC4, can compensate for the deficiency of the secretory mucin, MUC5AC, in goblet cell deficient mice. This compensation may explain why the symptoms of mucus threads can be found in some goblet deficiency diseases, and it may provide an alternative defensive mechanism in goblet cell deficiency.