(A) SADBE (1.5%, topical) was applied to the pigmented right ears of tamoxifen-induced Tyr-CreERT2
NrasQ61R/Q61R mutant mice 2 months after tamoxifen induction, whereas the pigmented left ears of the same animals were treated with acetone vehicle. Ear tissue images were obtained with a stereomicroscope, and dark brown particles indicate melanin. (B) Treatment scheme of adult Dct-Cre NrasQ61R/Q61R. Single-drug local therapy with 1.5% SADBE was administered topically to the right back. Acetone was applied topically to the left back of each SADBE-treated mouse as a vehicle control. All treatments were carried out three times per week (every other day), and the treated skin tissues were harvested 1 month after the first treatment to assess regression of melanocytic nevi (C, F). Tissue sections were immunostained for MelanA/MART1 (D, I). Melanin (black) detected by bright-field microscopy is shown in (E, J). (G) Treatment scheme of neonatal Dct-Cre NrasQ61R/Q61R mice. (H) Representative images of treated Dct-Cre NrasQ61R/Q61R mice unshaved (upper panel) and shaved (lower panel) are shown. White hairs were detectable in treated areas (H, upper panel red arrow). Regression of melanocytic nevi was detectable in treated areas (H, lower panel red arrow). The purple arrows in (H) indicate unchanged nevi in the nevus lesion treated with acetone vehicle. Yellow dashed lines in H demarcate the region treated with 1.5% SADBE. Stippled white lines in (D, E, I, J) separate the epidermis (epi) and hair follicles (HF) from the dermis.