Keratin 17 expression in the hard epithelial context of the hair and nail,and its relevance for the pachyonychia congenita phenotype

The hard-keratin-containing portion of the murine hair shaft displays a pos itive immunoreactivity with an antibody against the soft epithelial keratin , K17. The K17-expressing cell population is located in the medulla compart ment of the hair. Consistent with this observation, K17-containing cells al so occur in the presumptive medulla precursor cells located in the hair fol licle matrix. Western blot analysis of hair extracts prepared from a number of mouse strains confirms this observation and suggests that K17 expressio n in the hair shaft is a general trait in this species. The expression of K 17 in human hair extracts is restricted to eyebrow and facial hair samples. These are the major sites for the occurrence of the pili torti (twisted ha ir) phenotype in the type 2 (Jackson-Lawler) form of pachyonychia congenita , previously shown to arise from inherited K17 mutations. Given that all fo rms of pachyonychia congenita show an involvement of the nail, we compared the expression of the two other genes mutated in pachyonychia congenita dis eases, K6 and K16, with that of K17 in human nail. All three keratins are a bundantly expressed within the nail bed epithelium, whereas K17 protein is expressed in the nail matrix, which contains the epithelial cell precursors for the nail plate. Our data suggest a role for K17 in the formation and m aintenance of various skin appendages and directly support the concept that pachyonychia congenita is a disease of the nail bed.