title: Loss of keratin K2 expression causes aberrant aggregation of K10, hyperkeratosis, and inflammation.
abstract: Keratin K2 is one of the most abundant structural proteins of the epidermis; however, its biological significance has remained elusive. Here we show that suprabasal type II keratins, K1 and K2, are expressed in a mutually exclusive manner at different body sites of the mouse, with K2 being confined to the ear, sole, and tail skin. Deletion of K2 caused acanthosis and hyperkeratosis of the ear and the tail epidermis, corneocyte fragility, increased transepidermal water loss, and local inflammation in the ear skin. The loss of K2 was partially compensated by upregulation of K1 expression. However, a significant portion of K2-deficient suprabasal keratinocytes lacked a regular cytoskeleton and developed massive aggregates of the type I keratin, K10. Aggregate formation, but not hyperkeratosis, was suppressed by the deletion of both K2 and K10, whereas deletion of K10 alone caused clumping of K2 in ear skin. Taken together, this study demonstrates that K2 is a necessary and sufficient binding partner of K10 at distinct body sites of the mouse and that unbalanced expression of these keratins results in aggregate formation.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
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.
authors.forename: Julia
authors.initials: J
authors.lastname: Reichelt
authors.affiliation: Department of Genetics of Skin Carcinogenesis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Praetzel-Wunder
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Buchberger
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Minoo
authors.initials: M
authors.lastname: Ghannadan
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: leopold.eckhart@meduniwien.ac.at.
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004423:Ear; D005528:Foot; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053556:Keratin-1 / Q000378:metabolism; D053550:Keratin-10 / Q000235:genetics / Q000378:metabolism*; D053557:Keratin-2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013623:Tail
chemical_list: D053556:Keratin-1; D053557:Keratin-2; D053550:Keratin-10
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