Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Titel eines Journals oder einer Zeitschrift: | Journal of Allergy and Clinical Immunology | ||||
Verlag: | MOSBY-ELSEVIER | ||||
Ort der Veröffentlichung: | NEW YORK | ||||
Band: | 132 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 5 | ||||
Seitenbereich: | S. 1121-1129 | ||||
Datum: | 2013 | ||||
Institutionen: | Medizin > Lehrstuhl für Kinder- und Jugendmedizin | ||||
Identifikationsnummer: |
| ||||
Stichwörter / 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 | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 62117 |
Zusammenfassung
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 ...
Zusammenfassung
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.
Metadaten zuletzt geändert: 19 Dez 2024 08:32