Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1384-1391 |
| Number of pages | 8 |
| Journal | Journal of Investigative Dermatology |
| Volume | 132 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2012 |
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ASJC Scopus subject areas
- Dermatology
- Biochemistry
- Cell Biology
- Molecular Biology
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Keratin 16-null mice develop palmoplantar keratoderma, a hallmark feature of pachyonychia congenita and related disorders. / Lessard, Juliane C.; Coulombe, Pierre A.
In: Journal of Investigative Dermatology, Vol. 132, No. 5, 05.2012, p. 1384-1391.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Keratin 16-null mice develop palmoplantar keratoderma, a hallmark feature of pachyonychia congenita and related disorders
AU - Lessard, Juliane C.
AU - Coulombe, Pierre A.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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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U2 - 10.1038/jid.2012.6
DO - 10.1038/jid.2012.6
M3 - Article
C2 - 22336941
AN - SCOPUS:84859785430
VL - 132
SP - 1384
EP - 1391
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -