Koch P J, Mahoney M G, Cotsarelis G, Rothenberger K, Lavker R M, Stanley J R
Department of Dermatology, University of Pennsylvania School of Medicine, 415 Curie Blvd, Philadelphia, PA 19104, USA.
J Cell Sci. 1998 Sep;111 ( Pt 17):2529-37. doi: 10.1242/jcs.111.17.2529.
Little is known about the function of desmosomes in the normal structure and function of hair. Therefore, it was surprising that mice without desmoglein 3 (the autoantigen in pemphigus vulgaris) not only developed mucous membrane and skin lesions like pemphigus patients, but also developed hair loss. Analysis of this phenotype indicated that hair was normal through the first growth phase ('follicular neogenesis'). Around day 20, however, when the hair follicles entered the resting phase of the hair growth cycle (telogen), mice with a targeted disruption of the desmoglein 3 gene (DSG3-/-) lost hair in a wave-like pattern from the head to the tail. Hair then regrew and was lost again in the same pattern with the next synchronous hair cycle. In adults, hair was lost in patches. Gentle hair pulls with adhesive tape showed that anagen (growing) hairs were firmly anchored in DSG3-/- mice, but telogen hairs came out in clumps compared to that of DSG3+/- and +/+ littermates in which telogen hairs were firmly anchored. Histology of bald skin areas in DSG3-/- mice showed cystic telogen hair follicles without hair shafts. Histology of hair follicles in early telogen, just before clinical hair loss occurred, showed loss of cell adhesion (acantholysis) between the cells surrounding the telogen club and the basal layer of the outer root sheath epithelium. Electron microscopy revealed 'half-desmosomes' at the plasma membranes of acantholytic cells. Similar acantholytic histology and ultrastructural findings have been previously reported in skin and mucous membrane lesions of DSG3-/- mice and pemphigus vulgaris patients. Immunoperoxidase staining with an antibody raised against mouse desmoglein 3 showed intense staining on the cell surface of keratinocytes surrounding the telogen hair club in normal mice. Similar staining was seen in human telogen hair with an anti-human desmoglein 3 antibody. Finally, a scalp biopsy from a pemphigus vulgaris patient showed empty telogen hair follicles. These data demonstrate that desmoglein 3 is not only critical for cell adhesion in the deep stratified squamous epithelium, but also for anchoring the telogen hair to the outer root sheath of the follicle and underscore the importance of desmosomes in maintaining the normal structure and function of hair.
关于桥粒在毛发正常结构和功能中的作用，人们了解甚少。因此，令人惊讶的是，缺乏桥粒芯糖蛋白3（寻常型天疱疮中的自身抗原）的小鼠不仅出现了像天疱疮患者那样的黏膜和皮肤损伤，还出现了脱发。对这种表型的分析表明，在第一个生长阶段（“毛囊新生”）毛发是正常的。然而，在大约第20天时，当毛囊进入毛发生长周期的休止期（静止期）时，桥粒芯糖蛋白3基因靶向敲除的小鼠（DSG3-/-）会以从头部到尾部的波浪状模式脱发。然后毛发会重新生长，并在接下来的同步毛发周期中以相同模式再次脱落。在成年小鼠中，毛发会成片脱落。用胶带轻轻拔毛显示，在DSG3-/-小鼠中，生长期（生长中的）毛发牢固地锚定，但与DSG3+/-和+/+同窝小鼠相比，静止期毛发会成簇脱落，在DSG3+/-和+/+同窝小鼠中静止期毛发牢固地锚定。DSG3-/-小鼠秃发皮肤区域的组织学检查显示有不含毛干的囊性静止期毛囊。在临床脱发发生前的早期静止期毛囊的组织学检查显示，静止期毛球周围的细胞与外根鞘上皮基底层之间的细胞黏附丧失（棘层松解）。电子显微镜显示棘层松解细胞的质膜上有“半桥粒”。先前在DSG3-/-小鼠的皮肤和黏膜损伤以及寻常型天疱疮患者中也报道过类似的棘层松解组织学和超微结构发现。用针对小鼠桥粒芯糖蛋白3产生的抗体进行免疫过氧化物酶染色显示，在正常小鼠中，围绕静止期毛球的角质形成细胞的细胞表面有强烈染色。用抗人桥粒芯糖蛋白3抗体在人静止期毛发中也观察到类似染色。最后，对一名寻常型天疱疮患者的头皮活检显示有中空的静止期毛囊。这些数据表明，桥粒芯糖蛋白3不仅对深层复层鳞状上皮中的细胞黏附至关重要，而且对将静止期毛发锚定到毛囊的外根鞘也至关重要，并强调了桥粒在维持毛发正常结构和功能中的重要性。
