title: Targeted ablation of Arnt in mouse epidermis results in profound defects in desquamation and epidermal barrier function.
abstract: 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.
authors.affiliation: Department of Dermatology, Columbia University, New York, NY, USA.
authors.forename: Songmei
authors.initials: S
authors.lastname: Geng
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mezentsev
authors.forename: Sergey
authors.initials: S
authors.lastname: Kalachikov
authors.forename: Klaus
authors.initials: K
authors.lastname: Raith
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Roop
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Panteleyev
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D004817:Epidermis / Q000002:abnormalities* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D000091344:Filaggrin Proteins; D020869:Gene Expression Profiling; D018390:Gene Targeting; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D009928:Organ Specificity; D011498:Protein Precursors / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012873:Skin Diseases, Genetic / Q000378:metabolism
chemical_list: C497397:Arnt protein, mouse; D002518:Ceramides; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; C064554:loricrin; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C032253:involucrin