title: Missing C-terminal filaggrin expression, NFkappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis.
abstract: Filaggrin loss-of-function mutations resulting in C-terminal protein truncations are strong predisposing factors in human atopic dermatitis (AD). To assess the possibility of similar truncations in canine AD, an exclusion strategy was designed on 16 control and 18 AD dogs of various breeds. Comparative immunofluorescence microscopy was performed with an antibody raised against the canine filaggrin C-terminus and a commercial N-terminal antibody. Concurrent with human AD-like features such as generalized NFKB activation and hyperproliferation, four distinctive filaggrin expression patterns were identified in non-lesional skin. It was found that 10/18 AD dogs exhibited an identical pattern for both antibodies with comparable (category I, 3/18) or reduced (category II, 7/18) expression to that of controls. In contrast, 4/18 dogs displayed aberrant large vesicles revealed by the C-terminal but not the N-terminal antibody (category III), while 4/18 showed a control-like N-terminal expression but lacked the C-terminal protein (category IV). The missing C-terminal filaggrin in category IV strongly points towards loss-of function mutations in 4/18 (22%) of all AD dogs analysed.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Chervet
authors.forename: Arnaud
authors.initials: A
authors.lastname: Galichet
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Huijia
authors.initials: H
authors.lastname: Chen
authors.forename: Maja M
authors.initials: MM
authors.lastname: Suter
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Roosje
authors.forename: Eliane J
authors.initials: EJ
authors.lastname: Müller
mesh_terms: D000818:Animals; D001706:Biopsy; D049109:Cell Proliferation; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004285:Dogs; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D016328:NF-kappa B