Keratin 16–Null Mice Develop Palmoplantar Keratoderma, a Hallmark Feature of Pachyonychia Congenita and Related Disorders

Keratin 16 (KRT16 in human, Krt16 in mouse), a type I intermediate filament protein, is constitutively expressed in epithelial appendages and is induced in the epidermis upon wounding and other stressors. Mutations altering the coding sequence of KRT16 cause pachyonychia congenita (PC), a rare autos...

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Bibliographic Details
Published inJournal of investigative dermatology Vol. 132; no. 5; pp. 1384 - 1391
Main Authors Lessard, Juliane C., Coulombe, Pierre A.
Format Journal Article
LanguageEnglish
Published New York, NY Elsevier Inc 01.05.2012
Nature Publishing Group
Elsevier Limited
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Summary:Keratin 16 (KRT16 in human, Krt16 in mouse), a type I intermediate filament protein, is constitutively expressed in epithelial appendages and is induced in the epidermis upon wounding and other stressors. Mutations altering the coding sequence of KRT16 cause pachyonychia congenita (PC), a rare autosomal dominant disorder characterized by hypertrophic nail dystrophy, oral leukokeratosis, and palmoplantar keratoderma (PPK). PPK associated with PC is extremely painful and compromises patient mobility, making it the most debilitating PC symptom. In this study, we show that, although inherited in a recessive manner, the inactivation of Krt16 in mice consistently causes oral lesions as well as PPK-like hyperkeratotic calluses on Krt16−/− front and hind paws, which severely compromise the animals' ability to walk. Our findings call into question the view that PC-related PPK arises exclusively as a gain-of-function on account of dominantly acting mutated keratins, and highlight the key role of modifiers in the clinical heterogeneity of PC symptoms.
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ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2012.6