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• W2918448769 abstract "Abstract Background Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient ( FlgHrnr −/− ) mouse model lacking both genes including the intergenomic sequence. Results Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr −/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr −/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum . Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr −/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions Together, our FlgHrnr −/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions." @default.
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• W2918448769 date "2019-04-15" @default.
• W2918448769 modified "2023-10-18" @default.
• W2918448769 title "Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin‐hornerin (<i>FlgHrnr</i>^−/−) double‐deficient mice" @default.
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• W2918448769 doi "https://doi.org/10.1111/all.13756" @default.
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