Letter abstract
Nature Cell Biology 9, 461 - 469 (2007)
Published online: 11 March 2007 | doi:10.1038/ncb1560
Normal epidermal differentiation but impaired skin-barrier formation upon keratinocyte-restricted IKK1 ablation
Ralph Gareus1,2, Marion Huth2, Bernadette Breiden3, Arianna Nenci2, Nora Rösch2, Ingo Haase4, Wilhelm Bloch5, Konrad Sandhoff3 & Manolis Pasparakis1,2
The kinase IKK1 (also known as IKK
) was previously reported to regulate epidermal development and skeletal morphogenesis by acting in keratinocytes to induce their differentiation in an NF-
B independent manner1, 2, 3, 4, 5. Here, we show that mice with epidermal keratinocyte-specific IKK1 ablation (hereafter referred to as IKK1EKO) develop a normally differentiated stratified epidermis, demonstrating that the function of IKK1 in inducing epidermal differentiation is not keratinocyte-autonomous. Despite normal epidermal stratification, the IKK1EKO mice display impaired epidermal-barrier function and increased transepidermal water loss, due to defects in stratum corneum lipid composition and in epidermal tight junctions. These defects are caused by the deregulation of retinoic acid target genes, encoding key lipid modifying enzymes and tight junction proteins, in the IKK1-deficient epidermis. Furthermore, we show that IKK1-deficient cells display impaired retinoic acid-induced gene transcription, and that IKK1 is recruited to the promoters of retinoic acid-regulated genes, suggesting that one mechanism by which IKK1 controls epidermal-barrier formation is by regulating the expression of retinoic acid receptor target genes in keratinocytes.
- Institute for Genetics, Department of Mouse Genetics and Inflammation, University of Cologne, Zülpicher Str. 47, 50674 Cologne, Germany.
- EMBL Mouse Biology Unit, Via Ramarini 32, 00016 Monterotondo Scalo, Italy.
- LIMES, Membrane Biology and Lipid Biochemistry Unit, c/o Kekulè-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany.
- Department of Dermatology, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany.
- Department for Molecular and Cellular Sport Medicine, German Sport University Cologne, Carl-Diem-Weg 6, 50933 Cologne, Germany.
Correspondence to: Manolis Pasparakis1,2 e-mail: pasparakis@uni-koeln.de
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