Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development

Laura A. Hansen, Natalie Alexander, Margaret E. Hogan, John P. Sundberg, Andrzej Dlugosz, David W. Threadgill, Terry Magnuson, Stuart H. Yuspa

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Mice harboring a targeted disruption of the epidermal growth factor receptor (EGFR) allele exhibit a severely disorganized hair follicle phenotype, fuzzy coat, and systemic disease resulting in death before 3 weeks. This skin phenotype was reproduced in whole skin grafts and in grafts of EGFR null hair follicle buds onto nude mice, providing a model to evaluate the natural evolution of skin lacking the EGFR. Hair follicles in grafts of null skin did not progress from anagen to telogen and scanning electron micrografts revealed wavy, flattened hair fibers with cuticular abnormalities. Many of the EGFR null hair follicles in the grafted skin were consumed by an inflammatory reaction resulting in complete hair loss in 67% of the grafts by 10 weeks. Localization of follicular differentiation markers including keratin 6, transglutaminase, and the hair keratins mHa2 and hacl-1 revealed a pattern of premature differentiation within the null hair follicles. In intact EGFR null mice, proliferation in the interfollicular epidermis, but not hair follicles, was greatly decreased in the absence of EGFR. In contrast, 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 functions in the skin. It is important in delaying follicular differentiation, may serve to protect the hair follicle from immunological reactions, and modifies both normal and wound induced epidermal proliferation but seems dispensable for follicular proliferation.

Original languageEnglish (US)
Pages (from-to)1959-1975
Number of pages17
JournalAmerican Journal of Pathology
Volume150
Issue number6
StatePublished - Jun 16 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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