Lack of plakoglobin in epidermis leads to keratoderma

Deqiang Li, Wenjun Zhang, Ying Liu, Laura Haneline, Weinian Shou

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Loss-of-function mutation of Jup has been associated with Naxos disease, which is characterized by arrhythmogenic cardiomyopathy and the cutaneous disorder palmoplantar keratoderma. Previously, we have shown that genetic ablation of Jup in cardiomyocytes in mice leads to arrhythmogenic cardiomyopathy similar to Naxos disease in humans. Currently, to determine the pathogenesis of Naxos disease-associated keratoderma, we generated Jup mutant mice by inactivating Jup restrictively in keratinocytes. Jup mutant mice largely recapitulated the clinical features of human palmoplantar keratoderma: overcornification and thickening of the epidermis. Jup mutant mice also suffered skin ulceration and inflammation. Cell apoptosis and proliferation were significantly elevated in Jup mutant epidermis. Ultrastructural analyses revealed the disruption of the assembly of desmosomes and adherens junctions in Jup mutant epidermis. We also demonstrated the compensational increase in β-catenin at Jup mutant cell-cell junctions without altering its signaling activities. Our findings provide important insights for understanding the pathogenesis of human palmoplantar keratoderma.

Original languageEnglish
Pages (from-to)10435-10443
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number13
DOIs
StatePublished - Mar 23 2012

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gamma Catenin
Palmoplantar Keratoderma
Epidermis
Cardiomyopathies
Catenins
Ablation
Adherens Junctions
Desmosomes
Skin
Intercellular Junctions
Keratinocytes
Cardiac Myocytes
Apoptosis
Cell Proliferation
Inflammation
Mutation
Naxos disease

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Lack of plakoglobin in epidermis leads to keratoderma. / Li, Deqiang; Zhang, Wenjun; Liu, Ying; Haneline, Laura; Shou, Weinian.

In: Journal of Biological Chemistry, Vol. 287, No. 13, 23.03.2012, p. 10435-10443.

Research output: Contribution to journalArticle

Li, Deqiang ; Zhang, Wenjun ; Liu, Ying ; Haneline, Laura ; Shou, Weinian. / Lack of plakoglobin in epidermis leads to keratoderma. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 13. pp. 10435-10443.
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