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; 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

doi: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

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 TurnerVishnu 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 journal › Article › peer-review

120 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 language	English
Pages (from-to)	1121-9
Number of pages	9
Journal	Journal of Allergy and Clinical Immunology
Volume	132
Issue number	5
Early online date	29 Sept 2013
DOIs	https://doi.org/10.1016/j.jaci.2013.08.046
Publication status	Published - Nov 2013

Bibliographical note

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

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Saunders, S. P., Goh, C. S. M., Brown, S. J., Palmer, C. N. A., Porter, R. M., Cole, C., Campbell, L. E., Gierlinski, M., Barton, G. J., Schneider, G., Balmain, A., Prescott, A. R., Weidinger, S., Baurecht, H., Kabesch, M., Gieger, C., Lee, Y.-A., Tavendale, R., Mukhopadhyay, S., ... 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

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

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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. 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.",

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",

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}",

year = "2013",

month = nov,

doi = "10.1016/j.jaci.2013.08.046",

language = "English",

volume = "132",

pages = "1121--9",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby/Elsevier,",

number = "5",

}

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

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

C2 - 24084074

SN - 0091-6749

VL - 132

SP - 1121

EP - 1129

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

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