FOXN1 is critical for onycholemmal terminal differentiation in nude (Foxn1) mice.
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.
Mecklenburg
Lars
L
Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
Paus
Ralf
R
Halata
Zdenek
Z
Bechtold
Lesley S
LS
Fleckman
Philip
P
Sundberg
John P
JP
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology; D000091344:Filaggrin Proteins; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006724:Hoof and Claw / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D016023:Integrins / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053569:Keratin-15; D053555:Keratin-5; D015603:Keratinocytes / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D007633:Keratins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D009264:Nails, Malformed / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009831:Olfactory Mucosa / Q000166:cytology; D010159:Palate / Q000166:cytology; D013455:Sulfur / Q000378:metabolism; D013650:Taste Buds / Q000166:cytology; D014070:Tooth / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D051858:Forkhead Transcription Factors; D016023:Integrins; D007381:Intermediate Filament Proteins; C503940:KRT5 protein, human; D053569:Keratin-15; D053555:Keratin-5; D019394:Ki-67 Antigen; C492053:Krt15 protein, mouse; D014157:Transcription Factors; C090140:Whn protein; C001500:keratohyalin; D007633:Keratins; D013455:Sulfur