Keratin 9 Is Required for the Structural Integrity and Terminal Differentiation of the Palmoplantar Epidermis

Dun Jack Fu, Calum Thomson, Declan P. Lunny, Patricia J. Dopping-Hepenstal, John A. McGrath, Frances J. D. Smith, W. H. Irwin McLean, Deena M. Leslie Pedrioli (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    35 Citations (Scopus)

    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.
    Original languageEnglish
    Article numbern/a
    JournalJournal of Investigative Dermatology
    Volumen/a
    Early online date3 Oct 2013
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Keratin-9
    Structural integrity
    Epidermis
    Keratins
    Keratoderma, Palmoplantar, Epidermolytic
    Type I Keratin
    Bearings (structural)
    Alleles
    Hyperpigmentation
    Bony Callus
    Ablation
    Skin
    Genes
    Phenotype

    Keywords

    • EPPK
    • epidermolytic palmoplantar keratoderma
    • K9
    • keratin 9
    • Krt9−/−
    • K9-deficient
    • siRNA
    • small interfering RNA

    Cite this

    Fu, D. J., Thomson, C., Lunny, D. P., Dopping-Hepenstal, P. J., McGrath, J. A., Smith, F. J. D., ... Leslie Pedrioli, D. M. (2013). Keratin 9 Is Required for the Structural Integrity and Terminal Differentiation of the Palmoplantar Epidermis. Journal of Investigative Dermatology, n/a, [n/a]. https://doi.org/10.1038/jid.2013.356
    Fu, Dun Jack ; Thomson, Calum ; Lunny, Declan P. ; Dopping-Hepenstal, Patricia J. ; McGrath, John A. ; Smith, Frances J. D. ; McLean, W. H. Irwin ; Leslie Pedrioli, Deena M. / Keratin 9 Is Required for the Structural Integrity and Terminal Differentiation of the Palmoplantar Epidermis. In: Journal of Investigative Dermatology. 2013 ; Vol. n/a.
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    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.",
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    author = "Fu, {Dun Jack} and Calum Thomson and Lunny, {Declan P.} and Dopping-Hepenstal, {Patricia J.} and McGrath, {John A.} and Smith, {Frances J. D.} and McLean, {W. H. Irwin} and {Leslie Pedrioli}, {Deena M.}",
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    Keratin 9 Is Required for the Structural Integrity and Terminal Differentiation of the Palmoplantar Epidermis. / Fu, Dun Jack; Thomson, Calum; Lunny, Declan P.; Dopping-Hepenstal, Patricia J.; McGrath, John A.; Smith, Frances J. D.; McLean, W. H. Irwin; Leslie Pedrioli, Deena M. (Lead / Corresponding author).

    In: Journal of Investigative Dermatology, Vol. n/a, n/a, 2013.

    Research output: Contribution to journalArticle

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    T1 - Keratin 9 Is Required for the Structural Integrity and Terminal Differentiation of the Palmoplantar Epidermis

    AU - Fu, Dun Jack

    AU - Thomson, Calum

    AU - Lunny, Declan P.

    AU - Dopping-Hepenstal, Patricia J.

    AU - McGrath, John A.

    AU - Smith, Frances J. D.

    AU - McLean, W. H. Irwin

    AU - Leslie Pedrioli, Deena M.

    PY - 2013

    Y1 - 2013

    N2 - 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.

    AB - 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.

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    KW - keratin 9

    KW - Krt9−/−

    KW - K9-deficient

    KW - siRNA

    KW - small interfering RNA

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    ER -