title: Subcellular localization of desmosomal components is different between desmoglein3 knockout mice and pemphigus vulgaris model mice.
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.
  
  
  OBJECTIVE
  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 12.6nm toward the cytoplasm and the plakoglobin labeling density per desmosome decreased 31% in the desmosomes. In the PV model mice Desmoplakin shifted 22.7nm 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Saitama Municipal Hospital, 2460 Mimuro, Midori-ku, Saitama-shi, Saitama 336-8522, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiko
mesh_terms: D000051:Acantholysis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D051184:Desmoglein 3 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051180:Desmoplakins / Q000378:metabolism; D003896:Desmosomes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009061:Mouth Mucosa / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D010392:Pemphigus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051185:gamma Catenin / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D051184:Desmoglein 3; D051180:Desmoplakins; C495300:Dsg3 protein, mouse; C495295:Dsp protein, mouse; C495293:Jup protein, mouse; D051185:gamma Catenin