Proposed model of PMEL disruption in this study. (A) Disruption of pmela and pmelb resulted in complete golden plumage and hypopigmentation in eyes of tilapia. (B) Disruption of pmela and pmelb resulted in decreased and hypopigmented melanophores, and even guanine biosynthesis in not pigmented melanophores. Additionally, melanophores size was also heavily reduced in it. Disruption of pmela and pmelb also resulted in increased and larger sized xanthophores, which was another key reason for complete golden plumage. In wild-type fish, larger sized melanophores rejected the size-restricted xanthophores, whereas in PMEL-free mutants, the xanthophores with larger size than in wild-type fish pursuited the functionally restricted tiny melanophores. (C) Schematic view of melanin biosynthesis. Mitf as the key transcription factor for melanogenesis is responsible for cis-directing the mitf-axis downstream genes such as pmel. There are 4 phases of melanin, pmel was fundamental for both phases I–II and phases II–III melanin transition, thus hypopigmented melanophores were observed in PMEL disrupted tilapia. However, restoration of melanin biosynthesis was observed in PMEL disrupted tilapia, suggesting that additional collateral branches and some other key genes might be involved in melanin biosynthesis. The unknown gene was probably related to melanin biosynthesis from phase I to phase IV, and even lysosome biosynthesis. m, melanophores; m-m, melanophores with immature melanin; m-g, melanophores fulfilled with guanine; x, xanthophores.