Swirski, Sebastian and Röger, Carsten and Pienkowska-Schelling, Aldona and Ihlenburg, Cynthia and Fischer, Gösta and May, Oliver and Vorm, Mariann and Owczarek-Lipska, Marta and Neidhardt, John (2018) A Novel C-Terminal Mutation in Gsdma3 (C+/H−) Leads to Alopecia and Corneal Inflammatory Response in Mice. Investigative Opthalmology & Visual Science, 59 (1). p. 561. ISSN 1552-5783

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Official URL: http://dx.doi.org/10.1167/iovs.17-22658

Abstract

PURPOSE. Mutations in the gene encoding Gasdermin A3 (Gsdma3) have been described to cause severe skin phenotypes, including loss of sebaceous glands and alopecia, in mice. We discovered a novel C-terminal mutation in Gsdma3 in a new mouse line and characterized a less frequently reported corneal phenotype, likely caused by degeneration of Meibomian glands of the inner eyelid. METHODS. We used histologic methods to evaluate the effects of the C+/H- mutation on sebaceous gland and skin morphology as well as Meibomian glands of the inner eyelid and corneal tissue. Chromosomal aberrations were excluded by karyogram analyses. The mutation was identified by Sanger sequencing of candidate genes. RESULTS. Analyses of skin samples from affected mice confirmed the frequently reported phenotypes associated with mutations in Gsdma3: Degeneration of sebaceous glands and complete loss of pelage. Immunologic staining of corneal samples suggested an inflammatory response with signs of neovascularization in half of the affected older mice. While the corneal phenotype was observed at irregular time points, mainly after 6 months, its appearance coincided with a degeneration of Meibomian glands in the eyelids of affected animals. CONCLUSIONS. The mutation described herein is associated with inflammation and neovascularization of corneal tissue. Simultaneous degeneration of Meibomian glands in affected animals suggested a change in tear-film composition as the underlying cause for the corneal phenotype. Our data further support that different pathogenic mechanisms underlie some of the reported mutations in Gsdma3.

Item Type: Article
Additional Information: Publiziert mit Hilfe des DFG-geförderten Open Access-Publikationsfonds der Carl von Ossietzky Universität Oldenburg.
Uncontrolled Keywords: alopecia, meibomian gland, corneal inflammation, tears
Subjects: Technology, medicine, applied sciences > Medicine and health
Divisions: Faculty of Medicine and Health Sciences > Department of Human Medicine
Date Deposited: 11 Sep 2019 09:42
Last Modified: 11 Sep 2019 09:45
URI: https://oops.uni-oldenburg.de/id/eprint/4135
URN: urn:nbn:de:gbv:715-oops-42165
DOI: doi:10.1167/iovs.17-22658
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