GENETICALLY NULL MICE REVEAL A CENTRAL ROLE FOR EPIDERMAL GROWTH-FACTOR RECEPTOR IN THE DIFFERENTIATION OF THE HAIR FOLLICLE AND NORMAL HAIR DEVELOPMENT

Mice harboring a targeted disruption of the epidermal growth factor re ceptor (EGFR) allele exhibit a severely disorganized hair follicle phe notype, fuzzy cent, and systemic disease resulting in death before 3 w eeks. This skin phenotype was reproduced in whole skin grafts and in g rafts of EGFR null hair follicle buds onto nude mice, providing a mode l to evaluate the natural evolution of skin lacking the EGFR, Hair fol licles in grafts of null skin did not progress from anagen to telogen ann scanning electron micrografts revealed wavy, flattened hair fibers with cuticular abnormalities, Marry of the EGFR null hair follicles i n the grafted skirr rr,ere consumed by an inflammatory reaction result ing in complete hair loss in 67% of the grafts by 10 weeks, Localizati on of follicular differentiation markers including keratin 6, transglu taminase, ann the hair keratins mHa2 and hacl-1 revealed a pattern of premature differentiation within the null hair follicles. In intact EG FR null mice, proliferation in the interfollicular epidermis, but not hair follicles, was greatly decreased in the absence of EGFR. In contr ast, grafting of EGFR null skin resulted in a hyperplastic response in the epidermis that did not resolve even after 10 weeks, although the wound-induced hyperplasia in EGFR wild-type grafts had resolved within 3 to 4 weeks. Thus, epithelial expression of the EGFR has complex fun ctions in the skin, It is important in delaying follicular differentia tion, may serve to protect the hair follicle from immunological reacti ons, and modifies both normal and wound-induced epidermal proliferatio n but seems dispensable for follicular proliferation.