DESMOGLEIN-3 ANCHORS TELOGEN HAIR IN THE FOLLICLE

Little is known about the function of desmosomes in the normal structu re and function of hair. Therefore, it was surprising that mice withou t desmoglein 3 (the autoantigen in pemphigus vulgaris) not only develo ped mucous membrane and skin lesions like pemphigus patients, but also developed hair Loss. Analysis of this phenotype indicated that hair w as normal through the first growth phase ('follicular neogenesis'), Ar ound day 20, however, when the hair follicles entered the resting phas e of the hair growth cycle (telogen), mice with a targeted disruption of the desmoglein 3 gene (DSG3-/-) lost hair in a wave-like pattern fr om the head to the tail. Hair then regrew and was lost again in the sa me pattern with the next synchronous hair cycle. In adults, hair was l ost in patches. Gentle hair pulls with adhesive tape showed that anage n (growing) hairs were firmly anchored in DSG3-/- mice, but telogen ha irs came out in clumps compared to that of DSG3+/- and +/+ littermates in which telogen hairs were firmly anchored. Histology of bald skin a reas in DSG3-/- mice showed cystic telogen hair follicles without hair shafts. Histology of hair follicles in early telogen, just before cli nical 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-d esmosomes' at the plasma membranes of acantholytic cells. Similar acan tholytic histology and ultrastructural findings have been previously r eported in skin and mucous membrane lesions of DSG3-/- mice and pemphi gus vulgaris patients. Immunoperoxidase staining with an antibody rais ed against mouse desmoglein 3 showed intense staining on the cell surf ace of keratinocytes surrounding the telogen hair club in normal mice. Similar staining was seen in human telogen hair with an anti-human de smoglein 3 antibody. Finally, a scalp biopsy from a pemphigus vulgaris patient showed empty telogen hair follicles, These data demonstrate t hat desmoglein 3 is not only critical for cell adhesion in the deep st ratified 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 function of hair.