水体富营养化促进有毒蓝藻的水华爆发，产生的微囊藻毒素（MC-LR）可在鱼体内大量富集，从而严重污染鱼产品和危害人类健康。ABCC4转运蛋白作为介导哺乳动物对多毒物耐受性的主要因子，在毒物排泄中有着重要作用。我们前期的研究发现，过表达斑马鱼abcc4基因能显著增强ZFL（斑马鱼肝细胞系）对MC-LR胁迫的耐受性，推测其可能是参与鱼体对MC-LR排泄的重要因子。因此，本项目拟以斑马鱼为模型，研究转abcc4基因和abcc4基因敲除鱼对MC-LR的排泄特性及其作用机理。主要研究内容包括：（1）建立abcc4基因敲除的斑马鱼品系；（2）利用已有的转abcc4基因鱼和建立的abcc4基因敲除鱼，研究Abcc4蛋白过表达和缺失在MC-LR排泄中的作用及其机理。该研究结果将进一步揭示鱼类对MC-LR解毒和排泄的分子机制，同时为培育抗MC-LR积累的鱼类品种提供理论依据。

Microcystin-LR (MC-LR) are substantially released into a water body during a period of toxic cyanobacterial blooms that caused by eutrophication in aquatic environment. These toxicants can be accumulated in fish and transferred along the contaminated fish products and thus pose adverse effects on public health. ABCC4 transporter that mediates multi-xenobiotic resistance (MXR) in mammals, has been reported to exert an important function in toxicants excretion. Our previous studies have shown overexpression of zebrafish abcc4 gene can significantly improved the survivability of ZFL cells exposed to toxic MC-LR, which suggests it may be involved in the efflux of MC-LR in fish. In this study, we plan to research on the ability and underlying mechanism of abcc4-transgenetic and knockout zebrafish models in export of MC-LR. Main contents of this project include: (1) developing the abcc4 gene knockout zebrafish strains; (2) investigating the roles and mechanism of Abcc4-overexpression and knockout in the efflux of MC-LR by utilizing the developed abcc4-transgenic and knockout zebrafish. These results will not only be helpful to further reveal the molecular mechanism underlying the transport and detoxification of MC-LR in fish, but also can provide theoretical foundation for breeding fish strains in preventing accumulation of MC-LR.