A guide to assessing damage response pathways of the hair follicle: lessons from cyclophosphamide-induced alopecia in mice.
After chemical, biological, or physical damage, growing (i.e. anagen) hair follicles develop abnormalities that are collectively called hair follicle dystrophy. Comparatively lower follicular damage induces the "dystrophic anagen" response pathway (=prolonged, dystrophic anagen, followed by severely retarded follicular recovery). More severe follicular damage induces the dystrophic catagen pathway (=immediate anagen termination, followed by a dystrophic, abnormally shortened telogen and maximally fast follicular recovery). In order to recognize these distinct damage response strategies of the hair follicle in a clinical or histopathological context, we have used the well-established C57BL/6J mouse model of cyclophosphamide-induced alopecia to define pragmatic classification criteria for hair follicle dystrophy (e.g., structure and pigmentation of the hair shaft, location, and volume of ectopic melanin granules, distension of follicular canal, number of TdT-mediated dUTP nick end labeling positive keratinocytes in the hair bulb; neural cell-adhesion molecule immunoreactivity and alkaline phosphatase activity as markers for the level of damage to the follicular papilla). These classification criteria for hair follicle dystrophy are useful not only in chemotherapy-induced alopecia models, but also in the screening of drug-treated or mutant mice in a highly standardized, accurate, sensitive, reproducible, easily applicable, and quantifiable manner.
Institute of Cell Biology and Neurobiology, Center of Anatomy, Charite, Humboldt University, Berlin, Germany. Sven.Hendrix@charite.de
Sven
S
Hendrix
Bori
B
Handjiski
Eva M J
EM
Peters
Ralf
R
Paus
D000505:Alopecia / Q000139:chemically induced*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000009:adverse effects*; D017408:Guidelines as Topic; D006197:Hair / Q000473:pathology; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide