Increased epidermal growth factor receptor fsn/fsn mice

Epidermal growth factor receptors (EGF-Rs) are elevated in active human psoriatic lesions, but decrease in resolving lesions, Similar biologic responses in EGF-R levels have been demonstrated within human psoriatic skin grafted onto mice, We tested the hypothesis that flaky-skin mice (fsn/fsn), one proposed genetic animal model of psoriasis, would display EGF-R levels comparable to human psoriatic epidermis and show similar biologic responses, EGF-R levels were characterized in unperturbed sites in fsn/fsn skin and +/? skin by enzyme-linked immunosorbent assay, I-125-EGF binding, and immunostaining, Altered EGF-R levels were noted after mild trauma (tape stripping) or under resolving conditions (30 doses of 50 mJ/cm(2) ultraviolet B, 2.5 mg/kg oral cyclosporin A, or daily 30 mu g/ml topical EGF). Increased EGF-R immunostaining was observed in involved flaky epidermal sites before treatment, To determine whether a hyperproliferative (Koebner) reaction could be induced, we tape stripped fsn/fsn tail and non-flaky dorsal sites. EGF-R levels in dorsal epidermis increased by days 3-4 after injury by enzyme-linked immunoabsorbent assay methods, When fsn/fsn mice received one of three different treatments for 6 weeks, the skin returned to a normal phenotype both grossly and microscopically, Immunoreactive EGF-R in treated, but not untreated, sites decreased Co either normal or nondetectable levels, These data indicate that fsn/fsn mice exhibit an EGF-R profile identical to that of lesional and nonlesional human psoriatic epidermis, Modulations of the flaky phenotype in response to injury and three different treatments suggest that fsn/fsn is a useful in vivo model for examining new treatment modalities for psoriasiform skin diseases.