Saunders, Sean P. and Goh, Christabelle S. M. and Brown, Sara J. and Palmer, Colin N. A. and Porter, Rebecca M. and Cole, Christian and Campbell, Linda E. and Gierlinski, Marek and Barton, Geoffrey J. and Schneider, Georg and Balmain, Allan and Prescott, Alan R. and Weidinger, Stephan and Baurecht, Hansjoerg and Kabesch, Michael and Gieger, Christian and Lee, Young-Ae and Tavendale, Roger and Mukhopadhyay, Somnath and Turner, Stephen W. and Madhok, Vishnu B. and Sullivan, Frank M. and Relton, Caroline and Burn, John and Meggitt, Simon 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 Sandilands, Aileen and Fallon, Padraic 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). pp. 1121-1129. ISSN 0091-6749, 1097-6825
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; FLAKY TAIL MICE; ICHTHYOSIS VULGARIS; BARRIER FUNCTION; SUSCEPTIBILITY LOCI; SKIN INFLAMMATION; FILAGGRIN; DISEASE; PROTEIN; MUTATIONS; Allergy; association; atopic dermatitis; atopy; eczema; filaggrin; flaky tail; Matt; mattrin; mouse; mutation; Tmem79 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 08:58 |
| Last Modified: | 01 Apr 2020 08:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15768 |
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