Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 140, Issue 3, Pages 615-623Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2019.07.716
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Funding
- Lundbeck Foundation
- National Children's Research Centre
- Wellcome Trust
- UGent grant [GOA-01G01914]
- Lower Saxony Ministry of Science (OCCUDERM project)
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [ME 1708/4-1]
- American Heart Association [17GRNT32910002]
- National Science Center, Poland [2013/11/B/NZ1/00091, 2014/15/N/NZ5/01646, 2016/23/B/NZ5/00573, 2018/29/B/NZ4/00771]
- AMED [18gm1010001h0103, 18gm1010001h0003]
- JSPS [JP25461667]
- Lundbeck Foundation [R139-2012-12679] Funding Source: researchfish
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Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp(-/-)), filaggrin (Flg(ft/ft) and Flg(-/-)), filaggrin-hornerin (FlgHrnr(-/-)), and bleomycin hydrolase (Blmh(-/-)) were investigated. Sasp(-/-) and Flg(-/-) were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp(-/-). Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.
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