Experimental Induction of Alopecia Areata-Like Hair Loss in C3H/HeJ Mice Using Full-Thickness Skin Grafts

Alopecia areata (AA)-like hair loss in C3H/HeJ mice provides an excellent model for human AA disease research. The potential to induce mouse AA in normal haired C3H/HeJ mice at an early age or serially passage the AA phenotype was investigated by exchange of full-thickness skin grafts. Skin grafts from normal male and female C3H/HeJ, or severe combined immunodeficient C3H/SmnC Prkdcscid/J, mice onto AA-affected C3H/HeJ mice became inflamed and lost hair (28 of 28). Successful grafts from AA-affected C3H/HeJ mice induced hair loss in histocompatible C3H/OuJ mice (four of 13) and normal C3H/HeJ mice dependent on age (four of 17 at <31 d and 15 of 15 at >70 d). The AA phenotype was serially transmitted from induced AA mice to normal C3H/HeJ mice (nine of nine). Grafts from AA-affected C3H/HeJ mice onto C3H/SmnC Prkdcscid/J mice resulted in depigmented hair fiber regrowth and perifollicular neutrophil and eosinophil infiltrates but no hair loss (15 of 15). Sham grafting did not induce AA (none of 10). The finding that AA can be serially transferred from AA-affected C3H/HeJ mice to normal littermates and C3H/OuJ mice, indicates that an immune response against hair follicles can be induced with suitable stimuli. Conversely, skin grafts from normal C3H/HeJ, or C3H/SmnC Prkdcscid/J, mice rapidly lose hair due to lymphocyte, but not neutrophil and eosinophil, mediated inflammation. This AA induction method reproducibly provides large numbers of AA-affected mice to study the pathogenesis and treatment of human AA