Mice deficient for the epidermal dermokine β and γ isoforms display transient cornification defects

Area of Science:

• Dermatology
• Molecular Biology
• Genetics

Background:

• The human dermokine gene (DMKN) produces four isoform families with distinct expression patterns and cellular localizations.
• Secreted α, β, and γ isoforms are epidermis-restricted, with β and γ specific to granular keratinocytes.
• Intracellular δ isoforms are ubiquitously expressed.

Purpose of the Study:

• To characterize DMKN expression in mouse skin.
• To investigate the function of DMKN β and γ isoforms in skin development and barrier formation.
• To explore potential compensatory mechanisms in DMKN-deficient mice.

Main Methods:

• Analysis of DMKN gene expression in mouse skin.
• Generation and phenotypic analysis of homozygous mice null for DMKN β and γ isoforms.
• Biochemical analysis of skin components, including keratohyalin granules, cornified envelopes, profilaggrin, filaggrin, and involucrin.

Main Results:

• Mouse skin exhibited a less complex DMKN expression pattern than humans, lacking δ isoforms.
• DMKN β and γ null mice displayed temporary scaly skin, smaller keratohyalin granules, and increased cornified envelope sensitivity.
• Reduced profilaggrin and filaggrin, increased natural moisturizing factor components, and modified involucrin were observed.
• DMKN β and γ null mice showed significant overexpression of the DMKN α isoform.

Conclusions:

• DMKN β and γ isoforms are crucial for proper skin cornification and barrier function.
• The temporary phenotype suggests compensatory mechanisms, including DMKN α overexpression, are involved.
• This study enhances understanding of DMKN expression and function in mouse skin homeostasis.