QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 14 November 2006
doi: 10.1242/jcs.03282

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.03282v1 119/23/4901    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Geng, S. Articles by Panteleyev, A. A. Search for Related Content PubMed PubMed Citation Articles by Geng, S. Articles by Panteleyev, A. A. Social Bookmarking                         What's this?

Targeted ablation of Arnt in mouse epidermis results in profound defects in desquamation and epidermal barrier function

Songmei Geng^1,*,, Alexandre Mezentsev^1,, Sergey Kalachikov², Klaus Raith³, Dennis R. Roop⁴ and Andrey A. Panteleyev^1,

¹ Departmnet of Dermatology, Columbia University, New York, NY, USA
² Departmnet of Columbia Genome Center, Columbia University, New York, NY, USA
³ Institute of Pharmaceutics and Biopharmaceutics, Martin Luther University, Halle, Germany
⁴ Departments of Molecular and Cellular Biology and Dermatology, Baylor College of Medicine, Houston, TX, USA

Author for correspondence (e-mail: ap374{at}columbia.edu)

Accepted 27 September 2006

The molecular mechanisms of skin adaptation to the environmental stress are poorly understood. The aryl hydrocarbon receptor nuclear translocator (Arnt) lies at the intersection of several crucial adaptive pathways. Nevertheless, its role in adaptation of the skin to environmental stress has just begun to be unraveled. Here we show that Arnt is expressed in human and mouse skin in a developmentally dependent manner. Targeted K14-driven deletion of Arnt in the mouse epidermis resulted in early postnatal death, associated with a failure of epidermal barrier function. Gene expression profiling of Arnt-null mouse epidermis revealed upregulation of genes of the epidermal differentiation complex on mouse chromosome 3, including S100a genes (S100a8, S100a9, S100a10) and genes coding for small proline-rich proteins (Sprr1a, Sprr2i, Sprr2j, Sprrl1). HPTLC analysis showed significant accumulation of Cer[NS] and Cer[NH] ceramide species in Arnt-null epidermis, suggesting alterations in lipid metabolism. Continuous retention of corneosomes in Arnt-null epidermis that resulted in an abnormally dense corny layer and impaired desquamation was associated with upregulation of Slpi, an inhibitor of stratum corneum chymotryptic enzyme (SCCE) that plays a key role in corneosome degradation. The functional defects in Arnt-null mouse epidermis underscore the crucial role of Arnt in the maintenance of epidermal homeostasis, especially during the perinatal transition to the ex utero environment.

Key words: Corneosome, Ceramides, Epidermal differentiation complex, SCCE

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. H. Sutter, H. Yin, Y. Li, J. S. Mammen, S. Bodreddigari, G. Stevens, J. A. Cole, and T. R. Sutter EGF receptor signaling blocks aryl hydrocarbon receptor-mediated transcription and cell differentiation in human epidermal keratinocytes PNAS, March 17, 2009; 106(11): 4266 - 4271. [Abstract] [Full Text] [PDF]

				L. M. Sevilla, R. Nachat, K. R. Groot, J. F. Klement, J. Uitto, P. Djian, A. Maatta, and F. M. Watt Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier J. Cell Biol., December 31, 2007; 179(7): 1599 - 1612. [Abstract] [Full Text] [PDF]