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J Invest Dermatol. 2014 Mar;134(3):754-763. doi: 10.1038/jid.2013.356. Epub 2013 Aug 20.

Keratin 9 is required for the structural integrity and terminal differentiation of the palmoplantar epidermis.

Author information

1
Division of Molecular Medicine and Centre for Dermatology and Genetic Medicine, Colleges of Life Sciences and Medicine, Dentistry and Nursing, University of Dundee, Dundee, UK.
2
Microscopy Facility, College of Life Sciences, University of Dundee, Dundee, UK.
3
Epithelial Biology Group, Institute of Medical Biology, Immunos, Singapore.
4
Guy's and St Thomas' (GSTS) Pathology, St Thomas' Hospital, London, UK.
5
St John's Institute of Dermatology, King's College London, London, UK.
6
Division of Molecular Medicine and Centre for Dermatology and Genetic Medicine, Colleges of Life Sciences and Medicine, Dentistry and Nursing, University of Dundee, Dundee, UK. Electronic address: d.lesliepedrioli@dundee.ac.uk.

Abstract

Keratin 9 (K9) is a type I intermediate filament protein whose expression is confined to the suprabasal layers of the palmoplantar epidermis. Although mutations in the K9 gene are known to cause epidermolytic palmoplantar keratoderma, a rare dominant-negative skin disorder, its functional significance is poorly understood. To gain insight into the physical requirement and importance of K9, we generated K9-deficient (Krt9(-/-)) mice. Here, we report that adult Krt9(-/-)mice develop calluses marked by hyperpigmentation that are exclusively localized to the stress-bearing footpads. Histological, immunohistochemical, and immunoblot analyses of these regions revealed hyperproliferation, impaired terminal differentiation, and abnormal expression of keratins K5, K14, and K2. Furthermore, the absence of K9 induces the stress-activated keratins K6 and K16. Importantly, mice heterozygous for the K9-null allele (Krt9(+/-)) show neither an overt nor histological phenotype, demonstrating that one Krt9 allele is sufficient for the developing normal palmoplantar epidermis. Together, our data demonstrate that complete ablation of K9 is not tolerable in vivo and that K9 is required for terminal differentiation and maintaining the mechanical integrity of palmoplantar epidermis.

PMID:
23962810
PMCID:
PMC3923277
DOI:
10.1038/jid.2013.356
[Indexed for MEDLINE]
Free PMC Article

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