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Lookup NU author(s): Dr Sara Brown, Dr Stephen Turner, Professor Caroline Relton, Professor Sir John BurnORCiD, Dr Simon Meggitt, Professor Nick ReynoldsORCiD, Professor Heather Cordell
Background: Atopic dermatitis (AD) is a major inflammatory condition of the skin caused by inherited skin barrier deficiency, with mutations in the filaggrin gene predisposing to development of AD. Support for barrier deficiency initiating AD came from flaky tail mice, which have a frameshift mutation in Flg and also carry an unknown gene, matted, causing a matted hair phenotype.Objective: We sought to identify the matted mutant gene in mice and further define whether mutations in the human gene were associated with AD.Methods: A mouse genetics approach was used to separate the matted and Flg mutations to produce congenic single-mutant strains for genetic and immunologic analysis. Next-generation sequencing was used to identify the matted gene. Five independently recruited AD case collections were analyzed to define associations between single nucleotide polymorphisms (SNPs) in the human gene and AD.Results: The matted phenotype in flaky tail mice is due to a mutation in the Tmem79/Matt gene, with no expression of the encoded protein mattrin in the skin of mutant mice. Matt(ft) mice spontaneously have dermatitis and atopy caused by a defective skin barrier, with mutant mice having systemic sensitization after cutaneous challenge with house dust mite allergens. Meta-analysis of 4,245 AD cases and 10,558 population-matched control subjects showed that a missense SNP, rs6694514, in the human MATT gene has a small but significant association with AD.Conclusion: In mice mutations in Matt cause a defective skin barrier and spontaneous dermatitis and atopy. A common SNP in MATT has an association with AD in human subjects.
Author(s): Saunders SP, Goh CSM, Brown SJ, Palmer CNA, Porter RM, Cole C, Campbell LE, Gierlinski M, Barton GJ, Schneider G, Balmain A, Prescott AR, Weidinger S, Baurecht H, Kabesch M, Gieger C, Lee YA, Tavendale R, Mukhopadhyay S, Turner SW, Madhok VB, Sullivan FM, Relton C, Burn J, Meggitt S, Smith CH, Allen MA, Barker JNWN, Reynolds NJ, Cordell HJ, Irvine AD, McLean WHI, Sandilands A, Fallon PG
Publication type: Article
Publication status: Published
Journal: Journal of Allergy and Clinical Immunology
Year: 2013
Volume: 132
Issue: 5
Pages: 1121-1129
Print publication date: 01/11/2013
Online publication date: 29/09/2013
Acceptance date: 16/08/2013
Date deposited: 15/04/2015
ISSN (print): 0091-6749
ISSN (electronic): 1097-6825
Publisher: Mosby, Inc.
URL: http://dx.doi.org/10.1016/j.jaci.2013.08.046
DOI: 10.1016/j.jaci.2013.08.046
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