Increased epidermal growth factor receptor in fsn/fsn mice

Area of Science:

• Dermatology
• Molecular Biology
• Genetics

Background:

• Epidermal growth factor receptors (EGF-Rs) are elevated in active human psoriatic lesions.
• Biologic responses in EGF-R levels in human psoriatic skin grafts on mice mirror those in humans.
• The flaky-skin (fsn/fsn) mouse is a proposed genetic animal model for psoriasis.

Purpose of the Study:

• To determine if fsn/fsn mice exhibit EGF-R levels comparable to human psoriatic epidermis.
• To investigate if fsn/fsn mice show similar biologic responses to EGF-R modulation as observed in human psoriasis.
• To validate fsn/fsn mice as an in vivo model for studying psoriasiform skin diseases.

Main Methods:

• EGF-R levels were measured in fsn/fsn and wild-type (+/?) mouse skin using enzyme-linked immunosorbent assay, 125I-EGF binding, and immunostaining.
• fsn/fsn mice underwent mild trauma (tape stripping) and various treatments (UVB, cyclosporin A, topical EGF) to assess EGF-R modulation and phenotypic changes.
• Hyperproliferative (Koebner) reactions were induced and analyzed in fsn/fsn mice.

Main Results:

• Increased EGF-R immunostaining was observed in involved flaky epidermal sites before treatment.
• EGF-R levels in dorsal epidermis of fsn/fsn mice increased after tape stripping.
• Treatments normalized the flaky phenotype in fsn/fsn mice, with corresponding decreases in immunoreactive EGF-R.

Conclusions:

• fsn/fsn mice display an EGF-R profile identical to human psoriatic epidermis.
• Modulations of the flaky phenotype in fsn/fsn mice in response to injury and treatments are consistent with psoriasis.
• fsn/fsn mice serve as a valuable in vivo model for exploring new treatment strategies for psoriasiform skin diseases.