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Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr -/- ) double-deficient mice.
- Source :
-
Allergy [Allergy] 2019 Jul; Vol. 74 (7), pp. 1327-1339. Date of Electronic Publication: 2019 Apr 15. - Publication Year :
- 2019
-
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.<br />Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double-deficient (FlgHrnr <superscript>-/-</superscript> ) mouse model lacking both genes including the intergenomic sequence.<br />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 <superscript>-/-</superscript> mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr <superscript>-/-</superscript> 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 <superscript>-/-</superscript> mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions.<br />Conclusions: Together, our FlgHrnr <superscript>-/-</superscript> mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions.<br /> (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)
- Subjects :
- Adaptive Immunity
Animals
Biopsy
Calcium-Binding Proteins metabolism
Disease Models, Animal
Epidermis pathology
Filaggrin Proteins
Hypersensitivity metabolism
Immunity, Innate
Immunohistochemistry
Intermediate Filament Proteins metabolism
Mice
Mice, Knockout
Oxazolone pharmacology
Permeability
Phenotype
Calcium-Binding Proteins genetics
Epidermis immunology
Epidermis metabolism
Hypersensitivity genetics
Hypersensitivity immunology
Intermediate Filament Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1398-9995
- Volume :
- 74
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Allergy
- Publication Type :
- Academic Journal
- Accession number :
- 30828807
- Full Text :
- https://doi.org/10.1111/all.13756