FOXN1 is critical for onycholemmal terminal differentiation in nude (Foxn1) mice.
Document Type
Article
Publication Date
2004
Keywords
DNA-Binding-Proteins, Down-Regulation, Epithelial-Cells, Gene-Expression-Regulation, Hoof-and-Claw, Integrins, Intermediate-Filament-Proteins, Keratin, Keratinocytes, Ki-67-Antigen, Mice-Inbred-BALB-C, Mice-Nude, Microscopy-Electron-Scanning, Nails-Malformed, Olfactory-Mucosa, Palate, Sulfur, Taste-Buds, Tooth, Transcription-Factors
First Page
1001
Last Page
1011
JAX Source
J Invest Dermatol 2004 Dec; 123(6):1001-11.
Abstract
Nude mice have a mutation in the transcription factor Foxn1(nu), resulting in downregulation of hair keratins. Although hair follicles develop normally, the hair fibers become structurally weak, curl, and break off at the surface. Nails in nude mice are deformed, based on alterations of the onychocyte differentiation process. Elemental microanalysis of the nail plate reveals marked decreases in sulfur concentrations in the nude mouse nail plates. Immunohistochemistry shows a lack of keratin 1 expression in terminally differentiating keratinocytes of the nail matrix. Instead, the typical differentiation process of the matrix is altered toward an epidermis-like differentiation pattern, comprising the production of filaggrin-containing keratohyalin granules in cells resembling those of the stratum granulosum, which are never observed in normally haired mice. The nail plate has diffuse basophilic stippling. It is thinner than normal, weak, and in most Foxn1(nu)/Foxn1(nu) mice breaks where it separates from the hyponychium. These studies indicate that the Foxn1(nu) mutated gene has effects beyond downregulating keratin expression, including changes in filaggrin expression, and is critical for normal onycholemmal differentiation. The nails of nude mice provide new insights into the molecular controls of onychocyte differentiation, and they offer a useful model to investigate the pathogenesis of nail hypergranulosis, a common feature in human nail diseases.
Recommended Citation
Mecklenburg L,
Paus R,
Halata Z,
Bechtold LS,
Fleckman P,
Sundberg JP.
FOXN1 is critical for onycholemmal terminal differentiation in nude (Foxn1) mice. J Invest Dermatol 2004 Dec; 123(6):1001-11.