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 Sep 2013 |
| DOIs | |
| Publication status | Published - Nov 2013 |
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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
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 journal › Article
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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
C2 - 24084074
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 -