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  • The EMBO Journal (2000) 19, 3990 - 4003
  • doi:10.1093/emboj/19.15.3990

Skin and hair follicle integrity is crucially dependent on bold beta1 integrin expression on keratinocytes

Cord Brakebusch1, Richard Grose2, Fabio Quondamatteo3, Angel Ramirez4, Jose L. Jorcano4, Alison Pirro1, Marcus Svensson1, Rainer Herken3, Takako Sasaki5, Rupert Timpl5, Sabine Werner2 and Reinhard Fässler1

  1. Department of Experimental Pathology, Lund University, S-221 85 Lund, Sweden
  2. Swiss Federal Institute of Technology, Department of Cell Biology, CH-8093 Zürich, Switzerland
  3. Department of Histology, University of Göttingen, Göttingen, Germany
  4. Cell and Molecular Biology, CIEMAT, 28040 Madrid, Spain
  5. Max Planck Institute for Biochemistry, D-82152 Martinsried, Germany

Correspondence to:

Reinhard Fässler, E-mail: Reinhard.Fassler@pat.lu.se

Received 28 February 2000; Accepted 30 May 2000; Revised 15 May 2000

beta1 integrins are ubiquitously expressed receptors that mediate cell–cell and cell–extracellular matrix interactions. To analyze the function of beta1 integrin in skin we generated mice with a keratinocyte-restricted deletion of the beta1 integrin gene using the cre–loxP system. Mutant mice developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression of alpha6beta4 integrin, and the number of hemidesmosomes decreased. Basement membrane components were atypically deposited and, at least in the case of laminin-5, improperly processed, leading to disruption of the basement membrane and blister formation at the dermal–epidermal junction. In contrast, the integrity of the basement membrane surrounding the beta1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the maintenance of some, but not all basement membranes, in keratinocyte differentiaton and proliferation, and in the formation and/or maintenance of hemidesmosomes.

  • Keywords:

    • beta1 integrin,
    • epidermis,
    • hair follicle,
    • laminin-5,
    • tissue-specific knockout