Subcellular localization of desmosomal components is different between desmoglein3 knockout mice and pemphigus vulgaris model mice

Hitoshi Saito, Atsushi Shimizu, Kazuyuki Tsunoda, Masayuki Amagai, Akira Ishiko

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: The Desmoglein 3 (Dsg3) knockout mouse and pemphigus vulgaris (PV) mouse model present a similar type of supra-basal acantholysis, even though the subcellular mechanism is considered to be completely different. Objectives: To detect changes in the desmosomal molecular composition in Dsg3-/- mice and PV model mice to highlight the precise mechanism for acantholysis at an ultrastructural level. Methods: Using epithelia from Dsg3-/- mice, PV model mice, and their respective control mice, the desmosomal components were immunostained using a post-embedding immunogold labeling method, and their precise localization and the labeling density were statistically analyzed in the desmosomes before the occurrence of acantholysis. Results: Positive findings were detected in desmoplakin and plakoglobin. In the Dsg3-/- mice, the localization of desmoplakin shifted 12.6 nm toward the cytoplasm and the plakoglobin labeling density per desmosome decreased 31% in the desmosomes. In the PV model mice Desmoplakin shifted 22.7 nm more distantly from the plasma membrane but the labeling density per desmosome showed no significant difference, including plakoglobin. Similar results were obtained when analyzing the desmosomes of spinous cells in the mid-epidermis. Conclusion: These results showed the functional blocking of Dsg3 by autoantibody binding and the genetic defect of Dsg3 to induce different changes in the cytoplasmic desmosomal plaque proteins. A decrease in the level of plakoglobin is therefore not involved in the acantholysis in the PV model mice. The desmoplakin shift from the desmosomal plaque, which is induced by autoantibody binding under in vivo conditions in the PV model mouse, could be an early molecular change before the occurrence of acantholysis.

Original languageEnglish
Pages (from-to)108-115
Number of pages8
JournalJournal of Dermatological Science
Volume55
Issue number2
DOIs
Publication statusPublished - 2009 Aug 1

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Keywords

  • Adhesion molecule
  • Autoimmune
  • Desmosome
  • Electron microscopy
  • Immunogold
  • Ultrastructural localization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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