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Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects

Official URL:https://doi.org/10.1016/j.jaci.2013.08.046
PubMed:View item in PubMed
Creators Name:Saunders, S.P. and Goh, C.S.M. and Brown, S.J. and Palmer, C.N.A. and Porter, R.M. and Cole, C. and Campbell, L.E. and Gierlinski, M. and Barton, G.J. and Schneider, G. and Balmain, A. and Prescott, A.R. and Weidinger, S. and Baurecht, H. and Kabesch, M. and Gieger, C. and Lee, Y.A. and Tavendale, R. and Mukhopadhyay, S. and Turner, S.W. and Madhok, V.B. and Sullivan, F.M. and Relton, C. and Burn, J. and Meggitt, S. and Smith, C.H. and Allen, M.A. and Barker, J.N.W.N. and Reynolds, N.J. and Cordell, H.J. and Irvine, A.D. and McLean, W.H.I. and Sandilands, A. and Fallon, P.G.
Journal Title:Journal of Allergy and Clinical Immunology
Journal Abbreviation:J Allergy Clin Immunol
Volume:132
Number:5
Page Range:1121-1129
Date:November 2013
Keywords:Allergy, Association, Atopic Dermatitis, Atopy, Eczema, Filaggrin, Flaky Tail, Matt, Mattrin, Mutation, Tmem79, Animals, Mice
Abstract: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. Mattft 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.
ISSN:0091-6749
Publisher:Mosby (U.S.A.)
Item Type:Article

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