TRPV3 Gain-of-Function Mutation Impairs Differentiation of Hair Follicle Inner Root Sheath
TLDR A specific mutation in the TRPV3 gene causes hair follicle cells to develop improperly, leading to hair loss.
Gain-of-function mutations in TRPV3, such as the G568V mutation, were shown to impair hair follicle inner root sheath differentiation, leading to hair loss. In a knock-in mouse model, homozygous Trpv3G568V/G568V mice exhibited sparse hair within two weeks after birth, with hair shafts twisted and unable to penetrate the skin. Immunofluorescence revealed diminished trichohyalin and KRT71 in mutant hair follicles, indicating impaired inner root sheath cell differentiation. The hair loss was progressive, with mice becoming completely bald after three hair cycles. The study found that aberrant proliferation and ectopic expression of epidermal markers, along with the gradual loss of stem cells, led to the permanent disruption of hair follicles. These findings suggested that TRPV3 is crucial for inner root sheath keratinocyte differentiation, and its gain-of-function mutations cause hair loss by disrupting proliferation and differentiation programs, exhausting follicular keratinocyte stem cells.
