Loss of Normal Profilaggrin and Filaggrin in Flaky Tail (ft/ft) Mice: an Animal Model for the Filaggrin-Deficient Skin Disease Ichthyosis Vulgaris

摘要: Flaky tail (gene symbol ft) is an autosomal recessive mutation in mice that results a dry, flaky skin, and annular paw constrictions the neonatal period. Previous studies demonstrated ft maps to central region of mouse chromosome 3, vicinity epidermal differentiation complex, gene locus includes many nonkeratin genes expressed epidermis. In this study we report detailed characterization mouse. Affected homozygous ft/ft exhibit large, disorganized scales on marked attenuation granular layer, mild acanthosis, orthokeratotic hyperkeratosis. Biochemical analysis lacked normal high molecular profilaggrin (≈ 500 kDa), instead lower weight form (220 kDa) not proteolytically processed intermediates or filaggrin. Mutant irregular F-type keratohyalin granules contain profilaggrin, filaggrin was absent from cornified layers The expression keratins unchanged, whereas envelope proteins involucrin loricrin were increased Cultured keratinocytes also synthesized reduced amounts mRNA protein, demonstrating defect intrinsic cells. These findings demonstrate express abnormal polypeptide does F-granules We propose absence filaggrin, particular hygroscopic, filaggrin-derived amino acids are thought function hydration, underlies scaly skin characteristic mice. This animal model provides tool for understanding role may provide insight into basis filaggrin-deficient human disorder ichthyosis vulgaris.