title: Keratins K2 and K10 are essential for the epidermal integrity of plantar skin.
abstract: BACKGROUND
  K1 and K2 are the main type II keratins in the suprabasal epidermis where each of them heterodimerizes with the type I keratin K10 to form intermediate filaments. In regions of the ears, tail, and soles of the mouse, only K2 is co-expressed with K10, suggesting that these keratins suffice to form a mechanically resilient cytoskeleton.
  
  
  OBJECTIVE
  To determine the effects of the suppression of both main keratins, K2 and K10, in the suprabasal plantar epidermis of the mouse.
  
  
  METHODS
  Krt2(-/-) Krt10(-/-) mice were generated by crossing Krt2(-/-) and Krt10(-/-) mice. Epidermal morphology of soles of hind-paws was examined macroscopically and histologically. Immunofluorescence analysis and quantitative PCR analysis were performed to analyze the expression of keratins in sole skin of wildtype and Krt2(-/-) Krt10(-/-) mice. Highly abundant proteins of the sole stratum corneum were determined by electrophoretic and chromatographic separation and subsequent mass spectrometry.
  
  
  RESULTS
  K2 and K10 are the most prominent suprabasal keratins in normal mouse soles with the exception of the footpads where K1, K9 and K10 predominate. Mice lacking both K2 and K10 were viable and developed epidermal acanthosis and hyperkeratosis in inter-footpad epidermis of the soles. The expression of keratins K1, K9 and K16 was massively increased at the RNA and protein levels in the soles of Krt2(-/-) Krt10(-/-) mice.
  
  
  CONCLUSIONS
  This study demonstrates that the loss of the main cytoskeletal components of plantar epidermis, i.e. K2 and K10, can be only partly compensated by the upregulation of other keratins. The thickening of the epidermis in the soles of Krt2(-/-) Krt10(-/-) mice may serve as a model for pathomechanistic aspects of palmoplantar keratoderma.
authors.affiliation: Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: heinz.fischer@meduniwien.ac.at.
authors.forename: Heinz
authors.initials: H
authors.lastname: Fischer
authors.affiliation: Department of Genetics of Skin Carcinogenesis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Langbein
authors.affiliation: Institute of Cellular Medicine and North East England Stem Cell Institute, Newcastle University, Newcastle upon Tyne, UK; Divison of Experimental Dermatology and EB House Austria, Department of Dermatology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Reichelt
authors.affiliation: Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Buchberger
authors.affiliation: Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.affiliation: Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: leopold.eckhart@meduniwien.ac.at.
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D004817:Epidermis / Q000033:anatomy & histology / Q000502:physiology*; D005121:Extremities; D006801:Humans; D053556:Keratin-1 / Q000235:genetics / Q000378:metabolism; D053550:Keratin-10 / Q000235:genetics / Q000502:physiology*; D053536:Keratin-16 / Q000235:genetics / Q000378:metabolism; D053557:Keratin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053534:Keratin-9 / Q000235:genetics / Q000378:metabolism; D007645:Keratoderma, Palmoplantar / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007642:Keratosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C507441:KRT9 protein, mouse; D053556:Keratin-1; D053536:Keratin-16; D053557:Keratin-2; D053534:Keratin-9; C507491:Krt10 protein, mouse; D012333:RNA, Messenger; D053550:Keratin-10
keywords: Gene deletion; Keratin; Mouse model; Palmoplantar; Sole