Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model
Abstract Membrane-associated mucins (MAMs) are proposed to play critical roles at the ocular surface; however, in vivo evidence has been lacking. Here we investigate these roles by phenotyping of a Muc4 KO mouse. Histochemical analysis for expression of the beta-galactosidase transgene replacing Muc...
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| Format: | Article |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40491-0 |
| _version_ | 1827634458061176832 |
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| author | Rafael Martinez-Carrasco Satyanarayan Rachagani Surinder K. Batra Pablo Argüeso M. Elizabeth Fini |
| author_facet | Rafael Martinez-Carrasco Satyanarayan Rachagani Surinder K. Batra Pablo Argüeso M. Elizabeth Fini |
| author_sort | Rafael Martinez-Carrasco |
| collection | DOAJ |
| description | Abstract Membrane-associated mucins (MAMs) are proposed to play critical roles at the ocular surface; however, in vivo evidence has been lacking. Here we investigate these roles by phenotyping of a Muc4 KO mouse. Histochemical analysis for expression of the beta-galactosidase transgene replacing Muc4 revealed a spiraling ribbon pattern across the corneal epithelium, consistent with centripetal cell migration from the limbus. Depletion of Muc4 compromised transcellular barrier function, as evidenced by an increase in rose bengal staining. In addition, the corneal surface was less smooth, consistent with disruption of tear film stability. While surface cells presented with well-developed microprojections, an increase in the number of cells with fewer microprojections was observed. Moreover, an increase in skin-type keratin K10 and a decrease in transcription factor Pax6 was observed, suggesting an incipient transdifferentiation. Despite this, no evidence of inflammatory dry eye disease was apparent. In addition, Muc4 had no effect on signaling by toll-like receptor Tlr4, unlike reports for MUC1 and MUC16. Results of this study provide the first in vivo evidence for the role of MAMs in transcellular barrier function, tear film stability, apical epithelial cell architecture, and epithelial mucosal differentiation at the ocular surface. |
| first_indexed | 2024-03-09T15:13:38Z |
| format | Article |
| id | doaj.art-64eeb30c8e774af2a5129cb12c6ad5f6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:13:38Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-64eeb30c8e774af2a5129cb12c6ad5f62023-11-26T13:12:43ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-40491-0Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse modelRafael Martinez-Carrasco0Satyanarayan Rachagani1Surinder K. Batra2Pablo Argüeso3M. Elizabeth Fini4New England Eye Center, Tufts Medical Center and Department of Ophthalmology, Tufts University School of MedicineDepartment of Biochemistry & Molecular Biology, University of Nebraska Medical CenterDepartment of Biochemistry & Molecular Biology, University of Nebraska Medical CenterNew England Eye Center, Tufts Medical Center and Department of Ophthalmology, Tufts University School of MedicineNew England Eye Center, Tufts Medical Center and Department of Ophthalmology, Tufts University School of MedicineAbstract Membrane-associated mucins (MAMs) are proposed to play critical roles at the ocular surface; however, in vivo evidence has been lacking. Here we investigate these roles by phenotyping of a Muc4 KO mouse. Histochemical analysis for expression of the beta-galactosidase transgene replacing Muc4 revealed a spiraling ribbon pattern across the corneal epithelium, consistent with centripetal cell migration from the limbus. Depletion of Muc4 compromised transcellular barrier function, as evidenced by an increase in rose bengal staining. In addition, the corneal surface was less smooth, consistent with disruption of tear film stability. While surface cells presented with well-developed microprojections, an increase in the number of cells with fewer microprojections was observed. Moreover, an increase in skin-type keratin K10 and a decrease in transcription factor Pax6 was observed, suggesting an incipient transdifferentiation. Despite this, no evidence of inflammatory dry eye disease was apparent. In addition, Muc4 had no effect on signaling by toll-like receptor Tlr4, unlike reports for MUC1 and MUC16. Results of this study provide the first in vivo evidence for the role of MAMs in transcellular barrier function, tear film stability, apical epithelial cell architecture, and epithelial mucosal differentiation at the ocular surface.https://doi.org/10.1038/s41598-023-40491-0 |
| spellingShingle | Rafael Martinez-Carrasco Satyanarayan Rachagani Surinder K. Batra Pablo Argüeso M. Elizabeth Fini Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model Scientific Reports |
| title | Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model |
| title_full | Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model |
| title_fullStr | Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model |
| title_full_unstemmed | Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model |
| title_short | Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model |
| title_sort | roles unveiled for membrane associated mucins at the ocular surface using a muc4 knockout mouse model |
| url | https://doi.org/10.1038/s41598-023-40491-0 |
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