Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr(-/-)) double-deficient mice

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dc.contributor.authorRahrig, Sebastian
dc.contributor.authorDettmann, Judith M.
dc.contributor.authorBrauns, Birka
dc.contributor.authorLorenz, Verena N.
dc.contributor.authorBuhl, Timo
dc.contributor.authorKezic, Sanja
dc.contributor.authorElias, Peter M.
dc.contributor.authorWeidinger, Stephan
dc.contributor.authorMempel, Martin
dc.contributor.authorSchoen, Michael P.
dc.contributor.authorBraun, Andrea
dc.date.accessioned2021-12-23T16:23:33Z-
dc.date.available2021-12-23T16:23:33Z-
dc.date.issued2019
dc.identifier.issn01054538
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/14579-
dc.description.abstractBackground 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.
dc.description.sponsorshipDeutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [ME1708/4-1]; Bundesministerium fur Bildung und Forschung (BMBF)Federal Ministry of Education & Research (BMBF) [01GS 0818, 01GS 0812]; Lower Saxony Ministry of Science; Volkswagen FoundationVolkswagen; Deutsche Forschungsgemeinschaft, Grant/Award Number: ME1708/4-1; Bundesministerium fur Bildung und Forschung (BMBF), Grant/Award Number: NGFN, 01GS 0818, 01GS 0812; Lower Saxony Ministry of Science and the Volkswagen Foundation, Grant/Award Number: OCCUDERM
dc.language.isoen
dc.publisherWILEY
dc.relation.ispartofALLERGY
dc.subjectallergic contact dermatitis
dc.subjectAllergy
dc.subjectATOPIC-DERMATITIS
dc.subjectECZEMA
dc.subjectfilaggrin
dc.subjectGENE
dc.subjecthornerin
dc.subjectICHTHYOSIS VULGARIS
dc.subjectImmunology
dc.subjectMODEL
dc.subjectNATURAL MOISTURIZING FACTOR
dc.subjectOF-FUNCTION MUTATIONS
dc.subjectRISK-FACTORS
dc.subjectSKIN
dc.subjectskin barrier
dc.subjectSTRATUM-CORNEUM
dc.titleTransient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr(-/-)) double-deficient mice
dc.typejournal article
dc.identifier.doi10.1111/all.13756
dc.identifier.isiISI:000477968800010
dc.description.volume74
dc.description.issue7
dc.description.startpage1327
dc.description.endpage1339
dc.identifier.eissn13989995
dc.publisher.place111 RIVER ST, HOBOKEN 07030-5774, NJ USA
dcterms.isPartOf.abbreviationAllergy
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