Missing C-terminal filaggrin expression, NFkappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis

Chervet, L.; Galichet, A.; McLean, W.H.; Chen, H.; Suter, M.M.; Roosje, P.J.; Muller, E.J. (2010). Missing C-terminal filaggrin expression, NFkappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis. Experimental dermatology, 19(8), e343-6. Oxford: Blackwell 10.1111/j.1600-0625.2010.01109.x

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Dermatology

UniBE Contributor:

Galichet, Arnaud; Suter, Maja; Roosje, Pieternella and Müller, Eliane Jasmine

ISSN:

0906-6705

Publisher:

Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:36

Last Modified:

21 Jan 2014 15:05

Publisher DOI:

10.1111/j.1600-0625.2010.01109.x

Web of Science ID:

000280146200057

URI:

https://boris.unibe.ch/id/eprint/14308 (FactScience: 221222)

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