title: A novel mouse type I intermediate filament gene, keratin 17n (K17n), exhibits preferred expression in nail tissue.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Tong
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Coulombe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D015870:Gene Expression; D034582:Integumentary System / Q000502:physiology*; D007633:Keratins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D014018:Tissue Distribution
chemical_list: D007633:Keratins