模式生物斑马鱼在微量元素代谢研究中的应用

微量元素如铁、锌、铜等对维持生物体代谢和健康至关重要，其含量失衡会造成代谢异常甚至死亡，因此生物体存在复杂机制维持这些微量元素的稳态代谢平衡（homeostasis）。近年来国际上一些实验室尝试用模式脊椎生物斑马鱼来开展该领域的研究，展示出斑马鱼的特有优势。特别是大规模正向遗传学筛选的成功开展，一系列微量元素代谢异常的突变体（如：weissherbst、chardonnay、chianti、shiraz、gavi、calamity和catastrophe）相继发现，为研究离子代谢调控机制和相关疾病的发病机理，提供了整体动态的活体模型。铁代谢相关基因加，2J和grx5都己在斑马鱼中成功定位克隆，斑马鱼铜载体基因atp7a突变体calamity的深入研究，进一步阐明了Menkes病的发病机理。利用斑马鱼的优势，结合小鼠模型和人群来研究微量元素的体内稳态代谢平衡将是微量元素代谢机制研究的新方向。

Zebrafish as a vertebrate model for trace element metabolism studies

Trace element metabolism and homeostasis play key roles in many biological processes. Disruption of metabolism or homeostatic balance may cause disease and even death. Careful maintenance of trace element homeostasis is required in all biological systems. Over the last two decades, the zebrafish has become a model system for the study of mineral homeostasis. A series of zebrafish mutants with trace element metabolism defects have been identified by large-scale, forward genetic screens. They are weissherbst, chardonnay, chianti, shiraz, gavi, calamity and catastrophe. Studies of these mutants at the molecular and genetic levels have provided novelinsights into diseases associated with deregulation of mineral homeostasis and metabolism. Positional cloning of zebrafish mutants led to the identification offpnl and grx5, two genes that are involved in iron metabolism. Knowledge of the atp7a-deficient mutant calamity revealed the pathogenesis of Menkes disease. Here, we summarize the genes known to be involved in trace element homeostasis and metabolism. Future studies of trace element homeostasis using the zebrafish system might shed light on other diseases and allow exploration of potential therapeutic strategies.