Double mutation of <i>claudin‐1</i> and <i>claudin‐3</i> causes alopecia in infant mice
Double mutation of <i>claudin‐1</i> and <i>claudin‐3</i> causes alopecia in infant mice
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<i>claudin-1</i>和<i>claudin-3</i>双重突变导致幼年小鼠脱发
DOI：
10.1111/nyas.14980
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发表时间：
2023
影响因子：
5.2
通讯作者：
Tsukita Sachiko
中科院分区：
文献类型：
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作者：
Suzuki Koya;Yamaga Kosuke;Tokumasu Reitaro;Katsuno Tatsuya;Tanaka Hiroo;Chiba Shuhei;Yagi Takeshi;Katayama Ichiro;Tamura Atsushi;Murota Hiroyuki;Tsukita Sachiko
毛囊(Hf)经历生长、退化和休息的周期性阶段，与毛干相关，以维持毛皮。紧密连接蛋白CLDN-1的无义突变会导致人类脱发。因此，我们评估了CLDN在头发保留中的作用。在27个CLDN家族成员中，CLDN1、CLDN3、CLDN4、CLDN6和CLDN7在小鼠HFs的内隆起层、峡部和皮脂腺中表达。观察了Cldn1基因敲除较弱和Cldn3基因敲除小鼠(Cldn1Δ/ΔCldn3−/−)的毛发表型。虽然毛发生长正常，但Cldn1Δ/ΔCldn3−/−小鼠在第一个端原出现了显著的脱毛。CLDN1和CLDN3的同时缺失导致端原HFs的异常，例如具有多个细胞层的凸起中的上皮细胞膜结构异常分层，邻近皮脂腺的凸起定位错误，以及毛管扩张。伴随着缩短毛发保留期的端原HF异常，Cldn1Δ/ΔCldn3−/−小鼠Hfs周围的上皮细胞增殖加快，导致成人毛发加速再生。我们的发现表明，CLDN1和CLDN3可能通过维持HFs的适当分层结构来调节幼鼠的毛发保持，Hfs的缺乏可能会导致脱发。
Hair 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 inCldn1weaker knockdown andCldn3‐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 inCldn1Δ/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.