Hair Loss Caused by Gain-of-Function Mutant TRPV3 Is Associated with Premature Differentiation of Follicular Keratinocytes
TRPV3 gain-of-function mutation follicular keratinocytes trichohyalin keratins deiminated proteins apoptosis transcription regulators Foxn1 Msx2 Dlx3 Gata3 hair canal hair shaft outer root sheath hair cycles hair follicle stem cells miniaturized hair follicles keratin hair follicle hair cycle stem cells
TLDR A gene mutation causes early keratinocyte maturation leading to hair loss in Olmsted syndrome.
This study investigates the mechanism of hair loss in Olmsted syndrome caused by gain-of-function mutations in the TRPV3 gene using a mouse model with the G568V mutation. The mutation led to complete hair loss due to premature differentiation of follicular keratinocytes, characterized by early degeneration of trichohyalin and keratins, increased deiminated proteins, elevated apoptosis, and reduced transcription regulators (Foxn1, Msx2, Dlx3, and Gata3). These changes impaired hair canal and shaft formation, increased proliferation in the outer root sheath, accelerated hair cycles, reduced hair follicle stem cells, and miniaturized regenerated hair follicles. The findings suggest that targeting TRPV3 could be a potential therapeutic approach for hair loss conditions.
