title: Keratin 17 null mice exhibit age- and strain-dependent alopecia.
abstract: Onset of type I keratin 17 (K17) synthesis marks the adoption of an appendageal fate within embryonic ectoderm, and its expression persists in specific cell types within mature hair, glands, and nail. We report that K17 null mice develop severe alopecia during the first week postbirth, correlating with hair fragility, alterations in follicular histology, and apoptosis in matrix cells. These alterations are incompletely penetrant and normalize starting with the first postnatal cycle. Absence of a hair phenotype correlates with a genetic strain-dependent compensation by related keratins, including K16. These findings reveal a crucial role for K17 in the structural integrity of the first hair produced and the survival of hair-producing cells. Given that identical inherited mutations in this gene can cause either pachyonychia congenita or steatocystoma multiplex, the features of this mouse model suggest that this clinical heterogeneity arises from a cell type-specific, genetically determined compensation by related keratins.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: McGowan
authors.forename: Xuemei
authors.initials: X
authors.lastname: Tong
authors.forename: Emma
authors.initials: E
authors.lastname: Colucci-Guyon
authors.forename: Francina
authors.initials: F
authors.lastname: Langa
authors.forename: Charles
authors.initials: C
authors.lastname: Babinet
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Coulombe
mesh_terms: D000367:Age Factors; D000505:Alopecia / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005821:Genetic Techniques; D005838:Genotype; D020287:In Situ Nick-End Labeling; D007633:Keratins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D010641:Phenotype; D011995:Recombination, Genetic; D012867:Skin / Q000648:ultrastructure; D013045:Species Specificity; D013997:Time Factors
chemical_list: D007633:Keratins