Payne Elspeth, Look Thomas
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Br J Haematol. 2009 Aug;146(3):247-56. doi: 10.1111/j.1365-2141.2009.07705.x. Epub 2009 May 19.
The use of animal models has revealed important mechanisms relevant to the development and treatment of human cancer. In recent years the zebrafish has emerged as an exciting new organism in which to model leukaemogenesis. The zebrafish model has distinct advantages over other animal models, most notably a capacity for forward genetic studies and rapid small molecule screens which can be used to dissect novel genetic pathways contributing to the development of leukaemia. Additionally, the high fecundity and optical clarity of the zebrafish make it an attractive organism in which to directly visualize the localization and development of normal and abnormal haematopoiesis in vivo. Until recently, targeting mutations to specific genes was technically difficult in the zebrafish, but new technology using chimeric zinc fingers to create targeted gene knockouts has made reverse genetic modelling possible and promises to deliver many new and exciting models. This review summarizes the benefits of using the zebrafish to study leukaemogenesis, reviews current zebrafish models of specific leukaemias, and gives an overview of future direction for the zebrafish in the study of cancer.
动物模型的使用揭示了与人类癌症发生发展及治疗相关的重要机制。近年来，斑马鱼已成为一种令人兴奋的新型生物，可用于白血病发生的建模。斑马鱼模型相较于其他动物模型具有明显优势，最显著的是其具备进行正向遗传学研究和快速小分子筛选的能力，可用于剖析导致白血病发生的新遗传途径。此外，斑马鱼的高繁殖力和光学透明性使其成为一种有吸引力的生物，能够在体内直接观察正常和异常造血的定位及发育情况。直到最近，在斑马鱼中针对特定基因进行靶向突变在技术上还很困难，但利用嵌合锌指创建靶向基因敲除的新技术使反向遗传建模成为可能，并有望产生许多新的、令人兴奋的模型。本文综述了使用斑马鱼研究白血病发生的益处，回顾了当前特定白血病的斑马鱼模型，并概述了斑马鱼在癌症研究中的未来方向。
