EFFECTS OF MONOCLONAL ANTI-C-KIT ANTIBODY (ACK2) ON MELANOCYTES IN NEWBORN MICE

Previous studies indicate that c-Kit is required for postnatal melanoc yte development, To understand the precise mechanisms of c-Kit depende nce, we studied melanocyte development in newborn C57BL/6 mice by mean s of peritoneal injection of a monoclonal anti-c-Kit antibody (ACK2), which blocks c-Kit functions. The mice were injected once or more with ACK2 at various intervals after birth. In experiment 1, skin samples were examined on day 10 post-partum and in experiment 2 they were exam ined daily until day 10 post-partum, We studied melanocytes in the hai r follicles, epidermis, and dermis by light and electron microscopy wi th dopa reactions and immunohistochemistry. Epidermal melanocytes in u ntreated mice were dopa negative and c-Kit positive on day 0 post-part um but became dopa positive soon thereafter, In ACK2-treated mice, the earlier the mice received ACK2 injections after birth, the fewer mela nocytes they had, not only in the epidermis, but also in follicles. In these mice, melanocytes that had undergone apoptosis in the dermis an d the follicles were detected ultrastructurally. Some appeared to have produced tyrosinase, because they had dopa-positive melanosomes, Thes e results suggest that melanocytes in newborn mice are c-Kit dependent and undergo apoptosis when c-Kit receptors are blocked by ACK2 in the early days after birth. During this c-Kit-dependent period, melanocyt es differentiate from dopa negative to positive and migrate from the e pidermis to hair follicles.