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Development 128, 3843-3853 (2001)
© 2001 The Company of Biologists Limited

Requirement of NF-{kappa}B/Rel for the development of hair follicles and other epidermal appendices

Ruth Schmidt-Ullrich1,*, Toni Aebischer2, Joerg Hülsken1, Walter Birchmeier1, Uwe Klemm2 and Claus Scheidereit1

1 Max-Delbrück-Center of Molecular Medicine, Robert-Rössle Straße 10, 13092 Berlin, Germany
2 Max-Planck-Institute for Infection Biology, Schumannstraße 21/22, 10117 Berlin, Germany

*Author for correspondence (e-mail: rschmidt{at}mdc-berlin.de)

Accepted July 4, 2001

NF-{kappa}B/Rel transcription factors and I{kappa}B kinases (IKK) are essential for inflammation and immune responses, but also for bone-morphogenesis, skin proliferation and differentiation. Determining their other functions has previously been impossible, owing to embryonic lethality of NF-{kappa}B/Rel or IKK-deficient animals. Using a gene targeting approach we have ubiquitously expressed an NF-{kappa}B super-repressor to investigate NF-{kappa}B functions in the adult. Mice with suppressed NF-{kappa}B revealed defective early morphogenesis of hair follicles, exocrine glands and teeth, identical to Eda (tabby) and Edar (downless) mutant mice. These affected epithelial appendices normally display high NF-{kappa}B activity, suppression of which resulted in increased apoptosis, indicating that NF-{kappa}B acts as a survival factor downstream of the tumor necrosis factor receptor family member EDAR. Furthermore, NF-{kappa}B is required for peripheral lymph node formation and macrophage function.

Key words: Cre-loxP, Hypohidrotic ectodermal dysplasia (HED), Skin disease, Immunity, Drug targeting, Mouse




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© The Company of Biologists Ltd 2001