Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice

Area of Science:

• Dermatology
• Biophysics
• Genetics

Background:

• Corneocyte surface protrusions are linked to atopic dermatitis and filaggrin mutations.
• Natural moisturizing factors (NMFs) levels are inversely associated with these protrusions.

Purpose of the Study:

• To investigate the role of NMFs and filaggrin deficiency in skin surface texture alterations.
• To analyze the impact of genetic deficiencies in filaggrin synthesis/degradation on NMFs, cell stiffness, and corneocyte protrusions.

Main Methods:

• Examined five mouse models with genetic deficiencies: SASPase (Sasp-/-), filaggrin (Flgft/ft, Flg-/-), filaggrin-hornerin (FlgHrnr-/-), and bleomycin hydrolase (Blmh-/-).
• Utilized Atomic Force Microscopy (AFM) to measure elastic modulus and dermal texture index.
• Assessed NMF levels in the stratum corneum.

Main Results:

• All examined knockout mouse models showed increased corneocyte protrusions and decreased elastic modulus.
• NMF levels were reduced in most models, except for Sasp-/-.
• Dermal texture index correlated inversely with NMFs and elastic modulus.

Conclusions:

• Deficiencies in the filaggrin-NMF axis impair corneocyte mechanical properties in mice, with implications for human skin.
• Variations in NMFs and skin texture across different mouse models highlight the importance of selecting appropriate animal models for research.