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. 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.

Original languageEnglish
Pages (from-to)1121-9
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume132
Issue number5
Early online date29 Sep 2013
DOIs
Publication statusPublished - Nov 2013

Fingerprint

Atopic Dermatitis
Skin
Genes
Mutation
Single Nucleotide Polymorphism
Dermatitis
Tail
Dermatophagoides Antigens
Phenotype
Frameshift Mutation
Population Control
Hair
Meta-Analysis

Keywords

  • Animals
  • Dermatitis, Atopic
  • Gene Expression
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Proteins
  • Mice
  • Mutation
  • Phenotype
  • Physical Chromosome Mapping
  • Polymorphism, Single Nucleotide
  • Skin
  • Allergy
  • Association
  • Atopy
  • Eczema
  • Filaggrin
  • Matt
  • Mattrin
  • Tmem79

Cite this

Saunders, S. P., Goh, C. S. M., Brown, S. J., Palmer, C. N. A., Porter, R. M., Cole, C., ... Fallon, P. G. (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, 132(5), 1121-9. 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. 1121-9.

Research output: Contribution to journalArticle

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. 1121-9. https://doi.org/10.1016/j.jaci.2013.08.046
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. 1121-9.
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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. 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.",
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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}",
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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. 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.

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. 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.

KW - Animals

KW - Dermatitis, Atopic

KW - Gene Expression

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Membrane Proteins

KW - Mice

KW - Mutation

KW - Phenotype

KW - Physical Chromosome Mapping

KW - Polymorphism, Single Nucleotide

KW - Skin

KW - Allergy

KW - Association

KW - Atopy

KW - Eczema

KW - Filaggrin

KW - Matt

KW - Mattrin

KW - Tmem79

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 -