title: The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice.
abstract: Hair is maintained through a cyclic process that includes periodic regeneration of hair follicles in a stem cell-dependent manner. Little is known, however, about the cellular and molecular mechanisms that regulate the layered differentiation of the hair follicle. We have established a mutant mouse with a cyclic alopecia phenotype resulting from the targeted disruption of Sox21, a gene that encodes a HMG-box protein. These mice exhibit progressive hair loss after morphogenesis of the first hair follicle and become completely nude in appearance, but then show hair regrowth. Sox21 is expressed in the cuticle layer and the progenitor cells of the hair shaft in both mouse and human. The lack of this gene results in a loss of the interlocking structures required for anchoring the hair shaft in the hair follicle. Furthermore, the expression of genes encoding the keratins and keratin binding proteins in the hair shaft cuticle are also specifically down-regulated in the Sox21-null mouse. These results indicate that Sox21 is a master regulator of hair shaft cuticle differentiation and shed light on the possible causes of human hair disorders.
authors.affiliation: Division of Mammalian Development and Mammalian Genetics, National Institute of Genetics, Mishima, Shizuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Tanaka
authors.forename: Rie
authors.initials: R
authors.lastname: Saba
authors.forename: Satoru
authors.initials: S
authors.lastname: Matsuda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohyama
authors.forename: Hirotaka James
authors.initials: HJ
authors.lastname: Okano
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: D000505:Alopecia / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D006197:Hair / Q000166:cytology / Q000254:growth & development; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development; D007633:Keratins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055749:SOXB2 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
chemical_list: D055749:SOXB2 Transcription Factors; C484489:Sox21 protein, mouse; D007633:Keratins