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
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.
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