Nicastrin Deficiency Induces Tyrosinase-dependent Depigmentation and Skin Inflammation

Skin depigmentation diseases, such as vitiligo, are pigmentation disorders that often destroy melanocytes. However, their pathological mechanisms remain unclear and, therefore, promising treatments or prevention have been lacking. Here we demonstrate that a zebrafish insertional mutant showing a significant reduction of nicastrin transcript possesses melanosome maturation defect, Tyrosinase-dependent mitochondrial swelling and melanophore cell death. The depigmentation phenotypes are proven to be a result of γ-secretase inactivation. Furthermore, live imaging demonstrates that macrophages are recruited to and can phagocytose melanophore debris. Thus, we characterize a potential zebrafish depigmentation disease model, nicastrinhi1384 mutants, which can be used for further treatment/drug development of diseases related to skin depigmentation and/or inflammation.