Irhom2 Mutation Leads to Aberrant Hair Follicle Differentiation in Mice

The study identified a mutation in the iRhom2 gene in Uncv mice, leading to a hairless phenotype due to aberrant hair follicle differentiation. The iRhom2Uncv/Uncv mice showed dysplasia in hair follicles from postnatal day 3, with decreased hair matrix proliferation and abnormal differentiation of the hair shaft and inner root sheath. iRhom2 was found to be essential for the maturation of TNFα-converting enzyme (TACE), and its absence resulted in reduced levels of mature TACE in the skin. This disruption affected the activation of Notch1 and led to a significant down-regulation of Lef1 in the hair follicle matrix, establishing iRhom2 as a crucial regulator of hair follicle differentiation.