Double mutation of claudin‐1 and claudin‐3 causes alopecia in infant mice

Abstract

AbstractHair follicles (HFs) undergo cyclic phases of growth, regression, and rest in association with hair shafts to maintain the hair coat. Nonsense mutations in the tight junction protein claudin (CLDN)‐1 cause hair loss in humans. Therefore, we evaluated the roles of CLDNs in hair retention. Among the 27 CLDN family members, CLDN1, CLDN3, CLDN4, CLDN6, and CLDN7 were expressed in the inner bulge layer, isthmus, and sebaceous gland of murine HFs. Hair phenotypes were observed in Cldn1 weaker knockdown and Cldn3‐knockout (Cldn1Δ/ΔCldn3−/−) mice. Although hair growth was normal, Cldn1Δ/ΔCldn3−/− mice showed striking hair loss in the first telogen. Simultaneous deficiencies in CLDN1 and CLDN3 caused abnormalities in telogen HFs, such as an aberrantly layered architecture of epithelial cell sheets in bulges with multiple cell layers, mislocalization of bulges adjacent to sebaceous glands, and dilated hair canals. Along with the telogen HF abnormalities, which shortened the hair retention period, there was an enhanced proliferation of the epithelium surrounding HFs in Cldn1Δ/ΔCldn3−/− mice, causing accelerated hair regrowth in adults. Our findings suggested that CLDN1 and CLDN3 may regulate hair retention in infant mice by maintaining the appropriate layered architecture of HFs, a deficiency of which can lead to alopecia.