Requirement of NF-kappaB/Rel for the development of hair follicles and other epidermal appendices.
NF-kappaB/Rel transcription factors and IkappaB 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-kappaB/Rel or IKK-deficient animals. Using a gene targeting approach we have ubiquitously expressed an NF-kappaB super-repressor to investigate NF-kappaB functions in the adult. Mice with suppressed NF-kappaB 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-kappaB activity, suppression of which resulted in increased apoptosis, indicating that NF-kappaB acts as a survival factor downstream of the tumor necrosis factor receptor family member EDAR. Furthermore, NF-kappaB is required for peripheral lymph node formation and macrophage function.
Schmidt-Ullrich
R
R
Max-Delbrück-Center of Molecular Medicine, Robert-Rössle Strasse 10, 13092 Berlin, Germany. rschmidt@mdc-berlin.de
Aebischer
T
T
Hülsken
J
J
Birchmeier
W
W
Klemm
U
U
Scheidereit
C
C
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D003638:Deafness / Q000235:genetics / Q000503:physiopathology; D004439:Eccrine Glands / Q000002:abnormalities; D053331:Ectodysplasins; D053339:Edar Receptor; D004817:Epidermis / Q000196:embryology / Q000502:physiology*; D005088:Exocrine Glands / Q000503:physiopathology; D018859:Hair Follicle / Q000196:embryology / Q000473:pathology / Q000502:physiology*; D022781:Hepatocytes / Q000473:pathology; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D008208:Lymphatic System / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D016328:NF-kappa B / Q000502:physiology*; D020572:Oncogene Proteins v-rel / Q000378:metabolism; D010033:Otitis Media / Q000235:genetics / Q000503:physiopathology; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D014070:Tooth / Q000503:physiopathology
D053331:Ectodysplasins; C506019:Eda protein, mouse; D053339:Edar Receptor; C506009:Edar protein, mouse; D020672:I-kappa B Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D020572:Oncogene Proteins v-rel; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor