A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages

Numerous strains of mice with defined mutations display pronounced abnormal ities of hair follicle cycling, even in the absence of overt alterations of the skin and hair phenotype; however, in order to recognize even subtle, h air cycle-related abnormalities, it is critically important to be able to d etermine accurately and classify the major stages of the normal murine hair cycle, In this comprehensive guide, we present pragmatic basic and auxilia ry criteria for recognizing key stages of hair follicle growth (anagen), re gression (catagen) and quiescence (telogen) in C57BL/6NCrlBR mice, which ar e largely based on previous work from other authors, For each stage, a sche matic drawing and representative micrographs are provided in order to illus trate these criteria. The basic criteria can be employed for all mouse stra ins and require only routine histochemical techniques. The auxiliary criter ia depend on the immunohistochemical analysis of three markers (interleukin -1 receptor type I, transforming growth factor-beta receptor type II, and n eural cell-adhesion molecule), which allow a refined analysis of anatomical hair follicle compartments during all hair cycle stages. In contrast to pr ior staging systems, we suggest dividing anagen III into three distinct sub stages, based on morphologic differences, onset and progression of melanoge nesis, and the position of the dermal papilla in the subcutis, The computer -generated schematic representations of each stage are presented with the a im of standardizing reports on follicular gene and protein expression patte rns. This guide should become a useful tool when screening new mouse mutant s or mice treated with pharmaceuticals for discrete morphologic abnormaliti es of hair follicle cycling in a highly reproducible, easily applicable, an d quantifiable manner.