Bacterial conjunctivitis in Muc1 null mice

PURPOSE. In contrast to wild-type mice, genetically engineered Mucin1 (Muc1 ) null animals display a marked propensity for development of blepharitis a nd conjunctivitis. Molecular approaches confirmed the presence of Muc1 mRNA and protein in the conjunctival tissue of wild-type mice and identified th e bacterial species in Mud null symptomatic mice. METHODS. Muc1 null animals housed in a conventional facility were examined for visually apparent inflammation of the eye and surrounding tissue. Blood taken from overtly affected animals was assayed for antibodies to common m urine viral agents. Swabs of infected eyes and whole eye preparations were used to detect and speciate bacterial pathogens. Frozen sections of whole e ye, lid margin, and Harderian gland were immunostained with antibodies to M uc1 and cytokeratin 14, both epithelial cell markers. Northern blot analysi s and reverse transcription-polymerase chain reaction (RT-PCR) were perform ed on RNA isolated from conjunctiva and Harderian gland of wild-type mice t o compare relative levels of transcript. RESULTS. Student's unpaired t-test performed on the eye inflammation freque ncy of Mud null mice confirmed a statistical significance (P < 0.01) when c ompared to wild-type background animals housed in the same room. Analysis o f blood samples from affected Muc1 null animals detected no common murine v iral pathogens. Bacterial analysis of conjunctival swabs and whole eye prep arations demonstrated the presence of coagulase-negative Staphylococcus, St reptococcus type ct, and Corynebacterium group G2. Mud antibody staining of wild-type sections revealed the presence of Mud on conjunctival goblet and non-goblet cells and on the epithelium of the Harderian gland. Serial sect ions stained with cytokeratin 14 antibody confirmed the epithelial nature o f cells expressing the Mud protein. RNA from conjunctiva and Harderian glan d subjected to RT-PCR and northern blot analysis showed an abundance of Mud transcript in these tissues. CONCLUSIONS. Mud mRNA and protein are present in murine conjunctival and Ha rderian gland epithelia. Animals lacking Muc1 mRNA and protein are predispo sed to developing eye inflammation when compared to wild-type animals with an intact Muc1 gene. Mud appears to play a critical protective role at the ocular surface, presumably by acting as a barrier to infection by certain b acterial strains.