title: An adult passive transfer mouse model to study desmoglein 3 signaling in pemphigus vulgaris.
abstract: Evidence has accumulated that changes in intracellular signaling downstream of desmoglein 3 (Dsg3) may have a significant role in epithelial blistering in the autoimmune disease pemphigus vulgaris (PV). Currently, most studies on PV involve passive transfer of pathogenic antibodies into neonatal mice that have not finalized epidermal morphogenesis, and do not permit analysis of mature hair follicles (HFs) and stem cell niches. To investigate Dsg3 antibody-induced signaling in the adult epidermis at defined stages of the HF cycle, we developed a model with passive transfer of AK23 (a mouse monoclonal pathogenic anti-Dsg3 antibody) into adult 8-week-old C57Bl/6J mice. Validated using histopathological and molecular methods, we found that this model faithfully recapitulates major features described in PV patients and PV models. Two hours after AK23 transfer, we observed widening of intercellular spaces between desmosomes and EGFR activation, followed by increased Myc expression and epidermal hyperproliferation, desmosomal Dsg3 depletion, and predominant blistering in HFs and oral mucosa. These data confirm that the adult passive transfer mouse model is ideally suited for detailed studies of Dsg3 antibody-mediated signaling in adult skin, providing the basis for investigations on novel keratinocyte-specific therapeutic strategies.
authors.affiliation: Department of Molecular Dermatology, Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Schulze
authors.forename: Arnaud
authors.initials: A
authors.lastname: Galichet
authors.forename: Beyza S
authors.initials: BS
authors.lastname: Sayar
authors.forename: Anthea
authors.initials: A
authors.lastname: Scothern
authors.forename: Denise
authors.initials: D
authors.lastname: Howald
authors.forename: Hillard
authors.initials: H
authors.lastname: Zymann
authors.forename: Myriam
authors.initials: M
authors.lastname: Siffert
authors.forename: Denise
authors.initials: D
authors.lastname: Zenhäusern
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bolli
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koch
authors.forename: David
authors.initials: D
authors.lastname: Garrod
authors.forename: Maja M
authors.initials: MM
authors.lastname: Suter
authors.forename: Eliane J
authors.initials: EJ
authors.lastname: Müller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D049109:Cell Proliferation; D051184:Desmoglein 3 / Q000276:immunology / Q000502:physiology*; D003896:Desmosomes / Q000378:metabolism; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000502:physiology; D016259:Genes, myc; D051379:Mice; D008810:Mice, Inbred C57BL; D010392:Pemphigus / Q000209:etiology* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D051184:Desmoglein 3; C495300:Dsg3 protein, mouse; D066246:ErbB Receptors