Localization of the defect in skin diseases analyzed in the human skin graft-nude mouse model

Human skin can be grown away from its donor for prolonged periods as grafts on congenitally athymic "nude" mice. This system has been used to analyze the defect in several skin diseases, specifically to localize the site of the defect to the skin itself or to the epidermal or dermal components of the skin. In order to validate the use of the nude mouse human skin graft system in the analysis of skin defects, we have demonstrated that a systemic metabolic defect which involves the skin, namely essential fatty acid deficiency, can be differentiated from a defect residing primarily in the skin itself. Skin-marker systems have been developed for use with the nude mouse-human skin graft model to document the identity of human skin grafts and epidermal and dermal components of the grafts after prolonged periods of growth on the nude athymic mice. Y-body, a small fluorescent segment of the Y-chromosome seen in interphase cells, is used as a sex marker and serves to distinguish sex differences between the graft and the mouse recipient or between skin components of the graft. The ABH "blood-group" antigens are present on differentiated epidermal cell surfaces and identify the grafted epidermis according to the blood groups of the donor. In previous studies, lamellar ichthyosis was shown to be well maintained after prolonged periods of growth on nude athymic mice, indicating that the defect in this disease resides in the skin itself. Recombinant grafts composed of normal and lamellar ichthyosis epidermis and dermis further localize the defect to lamellar ichthyosis epidermis. Psoriasis is well maintained on the nude mouse-skin graft model. The epidermal hyperplasia and hyperproliferative epidermal cell kinetics of psoriasis are manifested in the grafts of active psoriasis maintained for prolonged periods on the nude mice, but the inflammatory component of psoriasis is absent. Recombinant graft studies utilizing normal and psoriatic epidermis and dermis demonstrate psoriasis only in recombinant grafts composed of both psoriatic epidermis and dermis. These studies indicate that psoriasis requires both psoriatic epidermis and dermis for its expression.