TY - JOUR
T1 - A novel mouse type I intermediate filament gene, keratin 17n (K17n), exhibits preferred expression in nail tissue
AU - Tong, Xuemei
AU - Coulombe, Pierre A.
N1 - Funding Information:
We are very grateful to Dr Kevin McGowan and Ms Kelsie Bernot for their efforts towards the isolation and characterization of a mouse genomic DNA contig. We thank Dr M. Bishr Omary for use of antibody L2A1. This work was supported by an NIAMS/NIH grant AR44232 to PAC.
PY - 2004/4
Y1 - 2004/4
N2 - Inactivating the type I keratin 17 gene (mK17) causes severe but reversible hair loss in a strain-dependent fashion in mouse (McGowan et al, Genes Dev. 16:1412, 2002). Missense mutations in human K17 give rise to two dominantly inherited disorders apparented to ectodermal dysplasias, pachyonychia congenita (PC), and steatocystoma multiplex (SM). In contrast to the null phenotype in mouse, marked lesions are seen in the nail and nail bed and sebaceous glands of PC and SM patients, respectively. In an effort to understand the lack of nail involvement in mK17 null mice, we discovered that the gene located immediately 5′ upstream from mK17 is functional and encodes a type I keratin protein highly analogous to mK17. mRNA and protein localization studies show that the expression of this novel gene is highly restricted and most prevalent in the nail bed and matrix, leading to its designation as mK17n (n stands for nail). Weak expression of mK17n also occurs in vibrissae follicles, in filiform and fungiform papillae of oral mucosa. These findings have direct implications for the mK17 null phenotype. Depending on the existence of a human ortholog or a functional equivalent, our findings may also provide a molecular explanation for several unusual aspects of hK17-based diseases.
AB - Inactivating the type I keratin 17 gene (mK17) causes severe but reversible hair loss in a strain-dependent fashion in mouse (McGowan et al, Genes Dev. 16:1412, 2002). Missense mutations in human K17 give rise to two dominantly inherited disorders apparented to ectodermal dysplasias, pachyonychia congenita (PC), and steatocystoma multiplex (SM). In contrast to the null phenotype in mouse, marked lesions are seen in the nail and nail bed and sebaceous glands of PC and SM patients, respectively. In an effort to understand the lack of nail involvement in mK17 null mice, we discovered that the gene located immediately 5′ upstream from mK17 is functional and encodes a type I keratin protein highly analogous to mK17. mRNA and protein localization studies show that the expression of this novel gene is highly restricted and most prevalent in the nail bed and matrix, leading to its designation as mK17n (n stands for nail). Weak expression of mK17n also occurs in vibrissae follicles, in filiform and fungiform papillae of oral mucosa. These findings have direct implications for the mK17 null phenotype. Depending on the existence of a human ortholog or a functional equivalent, our findings may also provide a molecular explanation for several unusual aspects of hK17-based diseases.
KW - Hair
KW - Pachyonychia congenita
KW - Skin
KW - Steatocystoma multiplex
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U2 - 10.1111/j.0022-202X.2004.22422.x
DO - 10.1111/j.0022-202X.2004.22422.x
M3 - Article
C2 - 15102087
AN - SCOPUS:2342575734
SN - 0022-202X
VL - 122
SP - 965
EP - 970
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -