Saunders, Sean P, Mukhopadhyay, Somnath and et al, (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

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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- eneration sequencing was used to identify the matted gene. Fiveindependently 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. Metaanalysis 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
Schools and Departments:	Brighton and Sussex Medical School > Brighton and Sussex Medical School Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects:	R Medicine > RJ Pediatrics > RJ0047.3 Genetic aspects
Depositing User:	Judy Keogh
Date Deposited:	15 Oct 2013 13:46
Last Modified:	24 Feb 2023 17:45
URI:	http://sro.sussex.ac.uk/id/eprint/46688

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