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

被引:128
作者
Saunders, Sean P. [1 ,2 ,3 ]
Goh, Christabelle S. M. [4 ]
Brown, Sara J. [4 ]
Palmer, Colin N. A. [5 ]
Porter, Rebecca M. [1 ,4 ]
Cole, Christian [4 ,6 ]
Campbell, Linda E. [4 ]
Gierlinski, Marek [6 ]
Barton, Geoffrey J. [6 ]
Schneider, Georg [9 ]
Balmain, Allan [7 ,10 ]
Prescott, Alan R.
Weidinger, Stephan [11 ]
Baurecht, Hansjoerg [11 ]
Kabesch, Michael [12 ]
Gieger, Christian [13 ]
Lee, Young-Ae [14 ,15 ]
Tavendale, Roger [5 ]
Mukhopadhyay, Somnath [16 ]
Turner, Stephen W. [17 ]
Madhok, Vishnu B. [8 ,18 ]
Sullivan, Frank M. [8 ,18 ]
Relton, Caroline
Burn, John
Meggitt, Simon [19 ]
Smith, Catherine H. [20 ]
Allen, Michael A. [20 ]
Barker, Jonathan N. W. N. [20 ]
Reynolds, Nick J. [21 ]
Cordell, Heather J.
Irvine, Alan D. [1 ,2 ,22 ]
McLean, W. H. Irwin [4 ]
Sandilands, Aileen [4 ]
Fallon, Padraic G. [1 ,2 ,3 ]
机构
[1] Univ Dublin Trinity Coll, Sch Med, Dublin 2, Ireland
[2] Our Ladys Childrens Hosp, Natl Childrens Res Ctr, Dublin, Ireland
[3] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Dublin 2, Ireland
[4] Univ Dundee, Ctr Dermatol & Genet Med, Dundee DD1 4HN, Scotland
[5] Univ Dundee, Biomed Res Inst, Dundee DD1 4HN, Scotland
[6] Univ Dundee, Bioinformat Res Grp, Dundee DD1 4HN, Scotland
[7] Univ Dundee, Div Cell Signalling & Immunol, Dundee DD1 4HN, Scotland
[8] Univ Dundee, Dundee DD1 4HN, Scotland
[9] ASTAR, Bioinformat Inst, Singapore, Singapore
[10] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
[11] Univ Hosp Schleswig Holstein, Dept Dermatol Allergy & Venerol, Kiel, Germany
[12] Childrens Hosp Regensburg, Dept Pediat Pneumol & Allergy, Regensburg, Germany
[13] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany
[14] Charite, D-13353 Berlin, Germany
[15] Max Delbruck Ctr Mol Med MDC, Berlin, Germany
[16] Royal Alexandra Childrens Hosp, Brighton & Sussex Med Sch, Acad Dept Paediat, Brighton, E Sussex, England
[17] Univ Aberdeen, Dept Child Hlth, Aberdeen AB9 1FX, Scotland
[18] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[19] Royal Victoria Infirm, Dept Dermatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
[20] Kings Coll London, St Johns Inst Dermatol, London WC2R 2LS, England
[21] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[22] Our Ladys Childrens Hosp, Dept Paediat Dermatol, Dublin, Ireland
基金
英国惠康基金; 英国医学研究理事会;
关键词
Allergy; association; atopic dermatitis; atopy; eczema; filaggrin; flaky tail; Matt; mattrin; mouse; mutation; Tmem79; GENOME-WIDE ASSOCIATION; BARRIER FUNCTION; SUSCEPTIBILITY LOCI; FILAGGRIN; SKIN; PROTEIN; MUTATIONS; HAIR; MODEL; MICE;
D O I
10.1016/j.jaci.2013.08.046
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1121 / 1129
页数:9
相关论文
共 31 条
[1]   Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: Changes in barrier function provide a sensitive indicator of disease activity [J].
Chamlin, SL ;
Kao, J ;
Frieden, IJ ;
Sheu, MY ;
Fowler, AJ ;
Fluhr, JW ;
Williams, ML ;
Elias, PM .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2002, 47 (02) :198-208
[2]   Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 1990-2010: A Systematic Review of Epidemiological Studies [J].
Deckers, Ivette A. G. ;
McLean, Susannah ;
Linssen, Sanne ;
Mommers, Monique ;
van Schayck, C. P. ;
Sheikh, Aziz .
PLOS ONE, 2012, 7 (07)
[3]   A common variant on chromosome 11q13 is associated with atopic dermatitis [J].
Esparza-Gordillo, Jorge ;
Weidinger, Stephan ;
Foelster-Holst, Regina ;
Bauerfeind, Anja ;
Ruschendorf, Franz ;
Patone, Giannino ;
Rohde, Klaus ;
Marenholz, Ingo ;
Schulz, Florian ;
Kerscher, Tamara ;
Hubner, Norbert ;
Wahn, Ulrich ;
Schreiber, Stefan ;
Franke, Andre ;
Vogler, Rainer ;
Heath, Simon ;
Baurecht, Hansjoerg ;
Novak, Natalija ;
Rodriguez, Elke ;
Illig, Thomas ;
Lee-Kirsch, Min-Ae ;
Ciechanowicz, Andrzej ;
Kurek, Michael ;
Piskackova, Tereza ;
Macek, Milan ;
Lee, Young-Ae ;
Ruether, Andreas .
NATURE GENETICS, 2009, 41 (05) :596-601
[4]   A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming [J].
Fallon, Padraic G. ;
Sasaki, Takashi ;
Sandilands, Aileen ;
Campbell, Linda E. ;
Saunders, Sean P. ;
Mangan, Niamh E. ;
Callanan, John J. ;
Kawasaki, Hiroshi ;
Shiohama, Aiko ;
Kubo, Akiharu ;
Sundberg, John P. ;
Presland, Richard B. ;
Fleckman, Philip ;
Shimizu, Nobuyoshi ;
Kudoh, Jun ;
Irvine, Alan D. ;
Amagai, Masayuki ;
McLean, W. H. Irwin .
NATURE GENETICS, 2009, 41 (05) :602-608
[5]   Pollen and eosinophilic esophagitis [J].
Fogg, MI ;
Ruchelli, E ;
Spergel, JM .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2003, 112 (04) :796-797
[6]   Intrinsically defective skin barrier function in children with atopic dermatitis correlates with disease severity [J].
Gupta, Jayanta ;
Grube, Emilie ;
Ericksen, Mark B. ;
Stevenson, Michelle D. ;
Lucky, Anne W. ;
Sheth, Anita P. ;
Assa'ad, Amal H. ;
Hershey, Gurjit K. Khurana .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 121 (03) :725-730
[7]   Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population [J].
Hirota, Tomomitsu ;
Takahashi, Atsushi ;
Kubo, Michiaki ;
Tsunoda, Tatsuhiko ;
Tomita, Kaori ;
Sakashita, Masafumi ;
Yamada, Takechiyo ;
Fujieda, Shigeharu ;
Tanaka, Shota ;
Doi, Satoru ;
Miyatake, Akihiko ;
Enomoto, Tadao ;
Nishiyama, Chiharu ;
Nakano, Nobuhiro ;
Maeda, Keiko ;
Okumura, Ko ;
Ogawa, Hideoki ;
Ikeda, Shigaku ;
Noguchi, Emiko ;
Sakamoto, Tohru ;
Hizawa, Nobuyuki ;
Ebe, Koji ;
Saeki, Hidehisa ;
Sasaki, Takashi ;
Ebihara, Tamotsu ;
Amagai, Masayuki ;
Takeuchi, Satoshi ;
Furue, Masutaka ;
Nakamura, Yusuke ;
Tamari, Mayumi .
NATURE GENETICS, 2012, 44 (11) :1222-1226
[8]   MECHANISMS OF DISEASE Filaggrin Mutations Associated with Skin and Allergic Diseases [J].
Irvine, Alan D. ;
McLean, W. H. Irwin ;
Leung, Donald Y. M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (14) :1315-1327
[9]   Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) - A widespread protein superfamily [J].
Jakobsson, PJ ;
Morgenstern, R ;
Mancini, J ;
Ford-Hutchinson, A ;
Persson, B .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (02) :S20-S24
[10]   Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice [J].
Kawasaki, Hiroshi ;
Nagao, Keisuke ;
Kubo, Akiharu ;
Hata, Tsuyoshi ;
Shimizu, Atsushi ;
Mizuno, Hideaki ;
Yamada, Taketo ;
Amagai, Masayuki .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2012, 129 (06) :1538-+