Keratin 13 deficiency causes white sponge nevus in mice.
Dev Biol
; 468(1-2): 146-153, 2020 12 01.
Article
em En
| MEDLINE
| ID: mdl-32758484
ABSTRACT
White sponge nevus (WSN) is a benign autosomal dominant disorder characterized by the formation of white spongy plaques in the oral mucosa. Keratin (KRT) 13 is highly expressed in the mucosa, and mutations in this gene have been commonly associated with WSN patients. However, it remains unknown whether there is a causal relationship between KRT13 mutations and WSN and what the underlying mechanisms might be. Here, we use mouse genetic models to demonstrate that Krt13 is crucial for the maintenance of epithelial integrity. Krt13 knockout mice show a WSN-like phenotype in several tissues, including the tongue, buccal mucosa, and esophagus. Transcriptome analyses uncover that Krt13 regulates a cohort of gene networks in tongue epithelial cells, including epithelial differentiation, immune responses, stress-activated kinase signaling, and metabolic processes. We also provide evidence that epithelial cells without Krt13 are susceptible to mechanical stresses experienced during postnatal life, resulting in unbalanced cell proliferation and differentiation. These data demonstrate that Krt13 is essential for maintaining epithelial homeostasis and loss of Krt13 causes the WSN-like phenotype in mice.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Proliferação de Células
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Células Epiteliais
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Leucoceratose da Mucosa Hereditária
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Queratina-13
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Mucosa Bucal
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Mutação
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Dev Biol
Ano de publicação:
2020
Tipo de documento:
Article