1. ¹Department of Dermatology, University of Cologne and Center for Molecular Medicine, University of Cologne (CMMC), Cologne, Germany
2. ²European Molecular Biology Laboratory, Mouse Biology Unit, Monterotondo, Rome, Italy
3. ³Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, ULP, Illkirch Cedex, France
4. ⁴Institut Clinique de la Souris (ICS), Illkirch Cedex, France

Correspondence: Dr Ingo Haase, Department of Dermatology, University of Cologne and Center for Molecular Medicine, University of Cologne (CMMC), Joseph-Stelzmann-Strasse 9, Cologne 50924, Germany. E-mail: Ingo.Haase@uni-koeln.de

Received 13 June 2005; Revised 9 July 2005; Accepted 10 September 2005; Published online 5 January 2006.

Abstract

Skin inflammation is a complex process that involves interactions between various cell types residing in different skin compartments. Using mice with conditionally targeted I kappa B kinase 2 (IKK2) alleles, we have previously shown that epidermal keratinocytes can play a dominant role in the initiation of an inflammatory reaction. In order to investigate long-term consequences of IKK2 deletion in adult skin, we have generated mice with floxed IKK2 alleles in which expression of a Tamoxifen-inducible Cre recombinase construct is targeted to epidermal keratinocytes (K14-Cre-ER^T2IKK2^fl/fl mice). K14-Cre-ER^T2IKK2^fl/fl mice are born normally and do not show signs of a skin disease until the age of 6 months. Deletion of IKK2 can be observed after Tamoxifen application to the back skin or spontaneously, without Tamoxifen application, in mice older than 6 months. This deletion is accompanied by dramatic, localized skin changes that are characterized by invasion of inflammatory cells, hair follicle disruption, and pseudoepitheliomatous hyperplasia of the epidermis, but not by tumor formation. The hyperplastic epithelium shows increased phosphorylation of signal transducer and activator of transcription 3 and extracellular signal-regulated protein kinase 1/2, typical features of psoriatic epidermis. Our results identify a primary role for IKK2 in the development of skin inflammation and confirm its requirement for the maintenance of skin homeostasis.