title: Keratin 9 is required for the structural integrity and terminal differentiation of the palmoplantar epidermis.
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.
authors: 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.
authors: Dun Jack
authors: DJ
authors: Fu
authors: Microscopy Facility, College of Life Sciences, University of Dundee, Dundee, UK.
authors: Calum
authors: C
authors: Thomson
authors: Epithelial Biology Group, Institute of Medical Biology, Immunos, Singapore.
authors: Declan P
authors: DP
authors: Lunny
authors: Guy's and St Thomas' (GSTS) Pathology, St Thomas' Hospital, London, UK.
authors: Patricia J
authors: PJ
authors: Dopping-Hepenstal
authors: St John's Institute of Dermatology, King's College London, London, UK.
authors: John A
authors: JA
authors: McGrath
authors: 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.
authors: Frances J D
authors: FJD
authors: Smith
authors: 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.
authors: W H
authors: WH
authors: Irwin McLean
authors: 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.
authors: Deena M
authors: DM
authors: Leslie Pedrioli
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology / Q000502:physiology*; D017495:Hyperpigmentation / Q000235:genetics / Q000473:pathology; D053534:Keratin-9 / Q000235:genetics* / Q000502:physiology*; D053546:Keratoderma, Palmoplantar, Epidermolytic / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C507441:KRT9 protein, mouse; D053534:Keratin-9; D034741:RNA, Small Interfering
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