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Y. Imbert, D.S. Darling, M.M. Jumblatt, G.N. Foulks, E.G. Couzin, P.S. Steele, W.W. Young, Jr.; Muc1 Splice Variants in Human Ocular Surface Tissues: Possible Differences Between Dry Eye Patients and Normal Controls . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5596.
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Mucins are highly glycosylated proteins that are vital to the maintenance of the ocular surface. Mucins act as lubricants, protectants and mediators of signal transduction. MUC 1 is a transmembrane mucin expressed at the ocular surface that contains a core region of 30–100 variable number of tandem repeats (VNTR) where the majority of the O–glycosylation sites are found. MUC 1 can be divided into small and large size classes of VNTR. At least 12 splice variants of MUC1 have been found in other tissues, but no splice variants have been reported in human ocular tissues. In this study we screened for the presence of MUC1 splice variants in human ocular tissues and in brush cytology samples collected from dry eye donors and normal controls.
Brush cytology was performed using sterile dacron polyester swabs. RT–PCR was used to identify MUC1 splice variants that were then confirmed by sequencing.
We here report the presence in some samples of human cornea, conjunctiva, and lacrimal gland of MUC1/B which features splicing directly between exons 1 and 2 and MUC1/A, a transcript that retains 27 bp from the 3' end of intron 1 and is predicted to add 9 amino acids to the MUC1 sequence upstream of the VNTR. The MUC1/A variant has been associated with a higher number of VNTR. Human cornea and conjunctiva both contain the MUC1/SEC splice variant that lacks the transmembrane domain and, therefore, results in a soluble, secreted form of MUC1. Cornea and conjunctiva also express MUC1/Y and MUC1/Z variants that lack the tandem repeat region. We have found a previously undescribed MUC1 variant transcript, termed MUC1/YI, that retains 99 bp from the 5' end of intron 1 and 27 bp from the 3' end of intron 1, resulting in a premature stop codon. Expression of the MUC1/A variant is lower in the conjunctival epithelium of dry eye patients as compared to normal controls. Western blotting confirmed that MUC1/A is associated with alleles containing the large size class of tandem repeats.
The human ocular surface expresses several MUC1 splice variants. We propose that one factor in susceptibility to dry eye disease may be the lengths of the MUC1 VNTR in conjunctival epithelium based on the rationale that longer VNTR provide better lubrication and greater protection of the ocular surface against inflammation.
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