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

Sean P Saunders, Christabelle S M Goh, Sara J Brown, Colin N A Palmer, Rebecca M Porter, Christian Cole, Linda E Campbell, Marek Gierlinski, Geoffrey J Barton, Georg Schneider, Allan Balmain, Alan R Prescott, Stephan Weidinger, Hansjörg Baurecht, Michael Kabesch, Christian Gieger, Young-Ae Lee, Roger Tavendale, Somnath Mukhopadhyay, Stephen W Turner & 14 others Vishnu B Madhok, Frank M Sullivan, Caroline Relton, John Burn, Simon Meggitt, Catherine H Smith, Michael A Allen, Jonathan N W N Barker, Nick J Reynolds, Heather J Cordell, Alan D Irvine, W H Irwin McLean, Aileen Sandilands, Padraic G Fallon

    Research output: Contribution to journalArticle

    69 Citations (Scopus)

    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. © 2013 American Academy of Allergy, Asthma & Immunology.

    Original languageEnglish
    Pages (from-to)1121-1129
    Number of pages9
    JournalJournal of Allergy and Clinical Immunology
    Volume132
    Issue number5
    DOIs
    Publication statusPublished - Nov 2013

    Fingerprint

    Atopic Dermatitis
    Skin
    Genes
    Mutation
    Single Nucleotide Polymorphism
    Dermatitis
    Tail
    Dermatophagoides Antigens
    Phenotype
    Frameshift Mutation
    Population Control
    Allergy and Immunology
    Hair
    Meta-Analysis
    Hypersensitivity
    Asthma

    Cite this

    Saunders, Sean P ; Goh, Christabelle S M ; Brown, Sara J ; Palmer, Colin N A ; Porter, Rebecca M ; Cole, Christian ; Campbell, Linda E ; Gierlinski, Marek ; Barton, Geoffrey J ; Schneider, Georg ; Balmain, Allan ; Prescott, Alan R ; Weidinger, Stephan ; Baurecht, Hansjörg ; Kabesch, Michael ; Gieger, Christian ; Lee, Young-Ae ; Tavendale, Roger ; Mukhopadhyay, Somnath ; Turner, Stephen W ; Madhok, Vishnu B ; Sullivan, Frank M ; Relton, Caroline ; Burn, John ; Meggitt, Simon ; Smith, Catherine H ; Allen, Michael A ; Barker, Jonathan N W N ; Reynolds, Nick J ; Cordell, Heather J ; Irvine, Alan D ; McLean, W H Irwin ; Sandilands, Aileen ; Fallon, Padraic G. / Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects. In: Journal of Allergy and Clinical Immunology. 2013 ; Vol. 132, No. 5. pp. 1121-1129.
    @article{73a8342eef0940a28dba9f6748833c76,
    title = "Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects",
    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. {\circledC} 2013 American Academy of Allergy, Asthma & Immunology.",
    author = "Saunders, {Sean P} and Goh, {Christabelle S M} and Brown, {Sara J} and Palmer, {Colin N A} and Porter, {Rebecca M} and Christian Cole and Campbell, {Linda E} and Marek Gierlinski and Barton, {Geoffrey J} and Georg Schneider and Allan Balmain and Prescott, {Alan R} and Stephan Weidinger and Hansj{\"o}rg Baurecht and Michael Kabesch and Christian Gieger and Young-Ae Lee and Roger Tavendale and Somnath Mukhopadhyay and Turner, {Stephen W} and Madhok, {Vishnu B} and Sullivan, {Frank M} and Caroline Relton and John Burn and Simon Meggitt and Smith, {Catherine H} and Allen, {Michael A} and Barker, {Jonathan N W N} and Reynolds, {Nick J} and Cordell, {Heather J} and Irvine, {Alan D} and McLean, {W H Irwin} and Aileen Sandilands and Fallon, {Padraic G}",
    note = "Copyright {\circledC} 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.",
    year = "2013",
    month = "11",
    doi = "10.1016/j.jaci.2013.08.046",
    language = "English",
    volume = "132",
    pages = "1121--1129",
    journal = "Journal of Allergy and Clinical Immunology",
    issn = "0091-6749",
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    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, Y-A, 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 2013, 'Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects', Journal of Allergy and Clinical Immunology, vol. 132, no. 5, pp. 1121-1129. https://doi.org/10.1016/j.jaci.2013.08.046

    Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects. / Saunders, Sean P; Goh, Christabelle S M; Brown, Sara J; Palmer, Colin N A; Porter, Rebecca M; Cole, Christian; Campbell, Linda E; Gierlinski, Marek; Barton, Geoffrey J; Schneider, Georg; Balmain, Allan; Prescott, Alan R; Weidinger, Stephan; Baurecht, Hansjörg; Kabesch, Michael; Gieger, Christian; Lee, Young-Ae; Tavendale, Roger; Mukhopadhyay, Somnath; Turner, Stephen W; Madhok, Vishnu B; Sullivan, Frank M; Relton, Caroline; Burn, John; Meggitt, Simon; Smith, Catherine H; Allen, Michael A; Barker, Jonathan N W N; Reynolds, Nick J; Cordell, Heather J; Irvine, Alan D; McLean, W H Irwin; Sandilands, Aileen; Fallon, Padraic G.

    In: Journal of Allergy and Clinical Immunology, Vol. 132, No. 5, 11.2013, p. 1121-1129.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects

    AU - Saunders, Sean P

    AU - Goh, Christabelle S M

    AU - Brown, Sara J

    AU - Palmer, Colin N A

    AU - Porter, Rebecca M

    AU - Cole, Christian

    AU - Campbell, Linda E

    AU - Gierlinski, Marek

    AU - Barton, Geoffrey J

    AU - Schneider, Georg

    AU - Balmain, Allan

    AU - Prescott, Alan R

    AU - Weidinger, Stephan

    AU - Baurecht, Hansjörg

    AU - Kabesch, Michael

    AU - Gieger, Christian

    AU - Lee, Young-Ae

    AU - Tavendale, Roger

    AU - Mukhopadhyay, Somnath

    AU - Turner, Stephen W

    AU - Madhok, Vishnu B

    AU - Sullivan, Frank M

    AU - Relton, Caroline

    AU - Burn, John

    AU - Meggitt, Simon

    AU - Smith, Catherine H

    AU - Allen, Michael A

    AU - Barker, Jonathan N W N

    AU - Reynolds, Nick J

    AU - Cordell, Heather J

    AU - Irvine, Alan D

    AU - McLean, W H Irwin

    AU - Sandilands, Aileen

    AU - Fallon, Padraic G

    N1 - Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

    PY - 2013/11

    Y1 - 2013/11

    N2 - 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. © 2013 American Academy of Allergy, Asthma & Immunology.

    AB - 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. © 2013 American Academy of Allergy, Asthma & Immunology.

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    U2 - 10.1016/j.jaci.2013.08.046

    DO - 10.1016/j.jaci.2013.08.046

    M3 - Article

    VL - 132

    SP - 1121

    EP - 1129

    JO - Journal of Allergy and Clinical Immunology

    JF - Journal of Allergy and Clinical Immunology

    SN - 0091-6749

    IS - 5

    ER -