Ultrastructural changes in mice actively producing antibodies to desmoglein 3 parallel those in patients with pemphigus vulgaris.
Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by autoantibodies against the desmosomal cadherins, desmogleins 1 and 3 (Dsg1, Dsg3) of which Dsg3 plays a major pathogenic role. We have previously generated a novel active disease mouse model for PV, which was produced by the transfer of splenocytes from Dsg3(-/-) mice, immunized with recombinant mouse Dsg3, into Rag2(-/-)-immunodeficient mice that express Dsg3. In this study, we undertook a further analysis of these PV model mice using electron microscopy (EM). We compared the ultrastructure of the epithelia of PV model mice with that of Dsg3(-/-) mice to highlight the mechanisms of blister formation in PV. These PV model mice showed the ultrastructural phenotype of PV, which is characterized by suprabasal acantholysis, rows of tombstone basal keratinocytes and half-desmosomes. Additionally, patchy hair loss was observed in PV model mice as in Dsg3(-/-) mice, and the ultrastructure of the telogen hair follicles was indistinguishable between PV model mice and Dsg3(-/-) mice. These results demonstrate that anti-Dsg3 autoantibodies interfere with the cell-cell adhesion of keratinocytes in PV model mice. In conclusion, our model mice closely represent the disease phenotype of PV at the ultrastructural level and can therefore be utilized not only as a clinical disease model but also to study the molecular mechanisms involved in blister formation in PV.
Shimizu
Atsushi
A
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Ishiko
Akira
A
Ota
Takayuki
T
Tsunoda
Kazuyuki
K
Koyasu
Shigeo
S
Amagai
Masayuki
M
Nishikawa
Takeji
T
D000051:Acantholysis / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D015820:Cadherins / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D051184:Desmoglein 3; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D018859:Hair Follicle / Q000648:ultrastructure; D008297:Male; D051379:Mice / Q000033:anatomy & histology*; D018345:Mice, Knockout / Q000235:genetics; D008854:Microscopy, Electron; D010392:Pemphigus / Q000276:immunology / Q000473:pathology*; D010641:Phenotype
D000906:Antibodies; D015820:Cadherins; D004268:DNA-Binding Proteins; C071894:DSG3 protein, human; D051184:Desmoglein 3; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2