title: Filaggrin in atopic dermatitis: flaky tail mice as a novel model for developing drug targets in atopic dermatitis.
abstract: The barrier abnormality, a loss-of-function mutation in the gene encoding filaggrin (FLG), which is linked to the incidence of atopic dermatitis (AD), is a recently discovered but important factor in the pathogenesis of AD. To investigate this issue in greater detail, mice that have a genetic defect (FLG) in barrier function will provide a model of AD closer to the human disease. Flaky tail (Flg(ft)) mice, essentially deficient in filaggrin, recently have been introduced to investigate the role of filaggrin on AD. These mice showed eczematous skin lesion in the steady state in line with increased of total IgE and Th17 expression in the skin. There is also an altered skin barrier function as a key element of AD either outside-to-inside barrier function or vice versa in Flg(ft) mice. Moreover, like human AD, these mice showed enhanced percutaneous allergen priming or response to cutaneous stimulants. Application of mite allergen in Flg(ft) mice, even without prior barrier disruption, remarkably enhanced both the clinical manifestations and the laboratory findings that correspond to indicators of human AD. These features of Flg(ft) mice allow us to investigate further the role of filaggrin in AD, and the knowledge obtained using these mice will be quite useful to develop a new therapeutic target for AD.
authors: Department of Dermatology, Kyoto University Graduate School of Medicine, Japan.
authors: Catharina Sagita
authors: CS
authors: Moniaga
authors: Kenji
authors: K
authors: Kabashima
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D013623:Tail / Q000473:pathology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins