TY - JOUR
T1 - Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice
AU - Thyssen, Jacob P.
AU - Jakasa, Ivone
AU - Riethmüller, Christoph
AU - Schön, Michael P.
AU - Braun, Andrea
AU - Haftek, Marek
AU - Fallon, Padraic G.
AU - Wróblewski, Jacek
AU - Jakubowski, Hieronim
AU - Eckhart, Leopold
AU - Declercq, Wim
AU - Koppes, Sjors
AU - Engebretsen, Kristiane A.
AU - Bonefeld, Charlotte
AU - Irvine, Alan D.
AU - Keita-Alassane, Sokhna
AU - Simon, Michel
AU - Kawasaki, Hiroshi
AU - Kubo, Akiharu
AU - Amagai, Masayuki
AU - Matsui, Takeshi
AU - Kezic, Sanja
PY - 2020/3
Y1 - 2020/3
N2 - 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 (Flgft/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.
AB - 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 (Flgft/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.
U2 - 10.1016/j.jid.2019.07.716
DO - 10.1016/j.jid.2019.07.716
M3 - Journal article
C2 - 31479664
AN - SCOPUS:85074345710
SN - 0022-202X
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
ER -