Heinz Fischer1, Lutz Langbein2, Julia Reichelt3, Maria Buchberger4, Erwin Tschachler4, Leopold Eckhart5. 1. Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: heinz.fischer@meduniwien.ac.at. 2. Department of Genetics of Skin Carcinogenesis, German Cancer Research Center, Heidelberg, Germany. 3. 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. 4. Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria. 5. Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: leopold.eckhart@meduniwien.ac.at.
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.
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: Jeffrey D Laskin; Gabriella Wahler; Claire R Croutch; Patrick J Sinko; Debra L Laskin; Diane E Heck; Laurie B Joseph Journal: Exp Mol Pathol Date: 2020-05-21 Impact factor: 3.362
Authors: Angelique N Voorberg; Hanna Niehues; Jart A F Oosterhaven; Geertruida L E Romeijn; Ivonne M J J van Vlijmen-Willems; Piet E J van Erp; Thomas H A Ederveen; Patrick L J M Zeeuwen; Marie L A Schuttelaar Journal: Exp Dermatol Date: 2021-07-21 Impact factor: 3.960