Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes that is caused by anti-
desmoglein 3 IgG autoantibodies. Recently, we generated an active disease mouse model for
pemphigus vulgaris by adoptive transfer of splenocytes from immunized
desmoglein 3-/- mice to Rag2-/- mice. In this study, we performed immunologic and histopathologic studies using this
pemphigus vulgaris model in mice and compared the gross and microscopic phenotypes of
pemphigus vulgaris model mice and
desmoglein 3-/- mice.
Pemphigus vulgaris model mice showed strong in vivo
IgG, and weak
IgA deposition on keratinocyte cell surfaces in stratified squamous epithelia, and produced circulating anti-
desmoglein 3 IgG antibodies without apparent cross-reactivity to
desmoglein 1, in
enzyme-linked
immunosorbent assays. The predominant
IgG subclass was
IgG1.
Pemphigus vulgaris model mice and
desmoglein 3-/- mice were almost indistinguishable in terms of both gross and microscopic findings. Both types of mice showed suprabasilar
acantholysis in the stratified squamous epithelia, including the oral mucous membranes and traumatized skin around the snout or paws; however, some
pemphigus vulgaris model mice demonstrated a more severe phenotype than
desmoglein 3-/- mice. The esophagus and forestomach were affected in some
pemphigus vulgaris model mice, but not in
desmoglein 3-/- mice. Furthermore, eosinophilic spongiosis, which is found in early
pemphigus vulgaris lesions in patients, was observed in
pemphigus vulgaris model mice but not in
desmoglein 3-/- mice.
Pemphigus vulgaris model mice reflect several of the histopathologic and immunologic features seen in
pemphigus vulgaris patients, and provide a valuable tool to investigate the pathophysiologic mechanisms of
pemphigus vulgaris.