Alteration of ocular surface mucins in MUC5AC-DTA transgenic mice.
OBJECTIVE
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.
Wang
I-Jong
IJ
Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
Yu
Chong-Jen
CJ
Hu
Fung-Rong
FR
D000818:Animals; D017209:Apoptosis; D015139:Blotting, Southern; D003228:Conjunctiva / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000378:metabolism*; D018628:Gene Dosage; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D055264:Mucin-4 / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism / Q000648:ultrastructure; D019076:Transgenes
D004167:Diphtheria Toxin; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055264:Mucin-4; D010446:Peptide Fragments; D012333:RNA, Messenger; C029795:diphtheria toxin fragment A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins