title: 5-Bromo-2'-deoxyuridine induced effluvium via p53-mediated CD326-positive keratinocyte apoptosis in C57BL/6 mice.
abstract: Anagen effluvium develops because of disturbances in the hair follicle cycle, leading to acute and severe hair loss in humans. The objective of this study was to establish a mouse model of anagen effluvium by 5-bromo-2'-deoxyuridine (BrdU) treatment, and evaluate the pathological changes and underlying mechanisms. We treated 9-10-day-old pups and 3-7-week-old C57BL/6 mice with BrdU. After successfully inducing hair loss in the neonatal pups, microscopic, immunohistochemical and flow cytometry analyses were conducted. BrdU induced early onset alopecia in neonates and caused epidermal thickening and hair shaft breakage. BrdU appeared to incorporate the CD326-positive keratinocyte layer and induced p53-related apoptosis. Keratinocyte apoptosis caused immune cell infiltration in the dermal region; M2 macrophages and neutrophils were dominant. The BrdU-induced hair loss was dose-dependent, and alopecia was visible at a dose range of 25-200 μg/g bodyweight. The BrdU-induced anagen effluvium mouse model is novel and easily established by administrating four simple BrdU injections to pups; these mice showed synchronized onset of alopecia symptoms with little individual variation. Moreover, this model showed an alopecia phenotype similar to that of human anagen effluvium with acute, severe and widespread hair loss.
authors.affiliation: Designed Animal and Transplantation Research Institute, Institute of Greenbio Research and Technology, Seoul National University, Pyeongchang, Korea.
authors.forename: Kyung-Jun
authors.initials: KJ
authors.lastname: Uh
authors.affiliation: Designed Animal and Transplantation Research Institute, Institute of Greenbio Research and Technology, Seoul National University, Pyeongchang, Korea.
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Hwang
authors.affiliation: Designed Animal and Transplantation Research Institute, Institute of Greenbio Research and Technology, Seoul National University, Pyeongchang, Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Bae
authors.affiliation: Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Jang
authors.affiliation: Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, Korea.
authors.forename: Su-Cheong
authors.initials: SC
authors.lastname: Yeom
mesh_terms: D000505:Alopecia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine; D004195:Disease Models, Animal; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D005260:Female; D018859:Hair Follicle / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000071858:Epithelial Cell Adhesion Molecule; D016159:Tumor Suppressor Protein p53; D001973:Bromodeoxyuridine
keywords: 5-bromo-2′-deoxyuridine; anagen effluvium; apoptosis; epithelial cell; p53