A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming.
Document Type
Article
Publication Date
2009
Keywords
Animals, Base-Sequence, Dermatitis-Atopic, Frameshift-Mutation, Genotype, Homozygote, Hypersensitivity, Ichthyosis-Vulgaris, Immunoglobulin-E, Intermediate-Filament-Proteins, Mice-Inbred-Strains, Models-Genetic, Molecular-Sequence-Data
First Page
602
Last Page
608
JAX Source
Nat Genet 2009 May; 41(5):602-8.
Abstract
Loss-of-function mutations in the FLG (filaggrin) gene cause the semidominant keratinizing disorder ichthyosis vulgaris and convey major genetic risk for atopic dermatitis (eczema), eczema-associated asthma and other allergic phenotypes. Several low-frequency FLG null alleles occur in Europeans and Asians, with a cumulative frequency of approximately 9% in Europe. Here we report a 1-bp deletion mutation, 5303delA, analogous to common human FLG mutations, within the murine Flg gene in the spontaneous mouse mutant flaky tail (ft). We demonstrate that topical application of allergen to mice homozygous for this mutation results in cutaneous inflammatory infiltrates and enhanced cutaneous allergen priming with development of allergen-specific antibody responses. These data validate flaky tail as a useful model of filaggrin deficiency and provide experimental evidence for the hypothesis that antigen transfer through a defective epidermal barrier is a key mechanism underlying elevated IgE sensitization and initiation of cutaneous inflammation in humans with filaggrin-related atopic disease.
Recommended Citation
Fallon PG,
Sasaki T,
Sandilands A,
Sundberg JP,
Presland RB,
Fleckman P,
Shimizu N,
Kudoh J,
Irvine AD,
et a.
A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet 2009 May; 41(5):602-8.