哺乳动物毛色决定的分子机制一直是生命科学领域的研究热点。家猫是哺乳动物毛色研究的一个新兴的动物模型。申请人前期关于家猫银色毛色遗传机制的研究鉴定出了一个全新的毛色决定基因BAG3，但BAG3如何调控动物黑色素合成进而影响动物毛色的分子机制尚处于未知状态。本项目拟从三个层面系统研究BAG3调控黑色素的分子机制：（1）在家猫层面研究BAG3在毛囊中的动态时空表达模式及对黑色素的影响；（2）在转基因小鼠层面验证BAG3影响毛色表型及机理；（3）在细胞水平最终验证BAG3调控黑色素的分子机制。本研究对已建立的哺乳动物黑色素细胞基因调控网络是一次重要的完善，能够揭示传统小鼠模型在黑色素细胞研究领域未能解决的一个“盲区”。此外，由于BAG3在各种肿瘤的增殖方面起着调控作用，因此本研究对于人类黑色素细胞病变导致的恶性黑色素瘤的发生和防治研究也具有重要的参考意义。

The mechanism underlying the mammal pigmentation determination has been a hotspot of biological studies for over two decades. The domestic cat has recently become a novel model species for mammal pigmentation studies. Our previous study determined a new pigmentation gene BAG3 is responsible for the silver coat color of domestic cats, however, the question remains how BAG3 regulates the biological process of melanin synthesis and further determines the coat color of domestic cats. In order to elucidate the mechanism of BAG3 regulating melanogenesis, studies will be performed at three different levels: (1) identifying the spatio-temporal expression pattern of BAG3 in the skin follicles of domestic cats and the influence of melanosome in silver cats; (2) verifying the coat color changes and the underlying mechanism in BAG3 transgenetic mouse; (3) revealing the molecular mechanism of BAG3 regulating melanogenesis at cell level. This study will complement the established pigmentation regulation network, and reveal the mechanism that laboratory mice cannot tell. In addition, because BAG3 plays an important role in tumor proliferation, this study may shed lights on the pathogenic mechanism and the potential gene therapy of melanoma.