| First Author | Rahrig S | Year | 2019 |
| Journal | Allergy | Volume | 74 |
| Issue | 7 | Pages | 1327-1339 |
| PubMed ID | 30828807 | Mgi Jnum | J:345841 |
| Mgi Id | MGI:7611756 | Doi | 10.1111/all.13756 |
| Citation | Rahrig S, et al. (2019) Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr(-/-) ) double-deficient mice. Allergy 74(7):1327-1339 |
| abstractText | 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. |
