实验小鼠在人类癌症研究中的应用及其进展

Application and Recent Advances of Laboratory Mouse in Human Cancer Research

小鼠是生物医学研究中使用数量最多的哺乳类实验动物。小鼠体型小,繁殖力强,饲养成本低。更重要的是小鼠遗传资源丰富,已经成功培育478个近交系,通过自发突变、诱发突变和转基因技术等途径培育并保存了2000多个突变品系。作为人类基因组计划的一部分,小鼠基因组序列的测定也已经完成,发现小鼠遗传组成与人类非常相似。人类利用小鼠模型进行癌症研究也有100多年的历史了,小鼠大量的遗传变异可作为研究人类癌症的借鉴。特别是近20多年来,培育成功的转基因(transgene)、基因敲除(knock-out)、基因封闭(knock-down)等遗传工程小鼠(geneticallyengineeredmouse,GEM)模型,使我们对人类癌症发生有了深刻的认识,为评估癌症的诊断方法、革新预防和治疗方案提供了一个很有价值的平台。本文着重介绍了小鼠的生物学特性、癌症研究中常用的小鼠模型、GEM模型、建立复杂GEM模型所采用的最新策略及取得的最新进展等,分析了小鼠模型的局限性。

Mouse is the most popular laboratory animal in medical research. It is small in size with high fertility ability, and its cost is low. The most important characteristics of mouse are their abundant genetic resources. Up to now, 478 inbred strains have been cultured, and more than 2 000 mutant strains have been established by either spontaneous, inducible methods or transgenic technology, and conserved in world. As a parallel part of human genome project (HGP), the DNA sequencing of entire genome of mouse has been completed, which reveals that there is a high genetic similarity between mouse and human. As an animal model, mouse has been used for human cancer research for over one century because of the presence of numerous genetic variants. Over the past 20 years, genetically engineered mouse (GEM), including transgenic mouse, knock-out mouse, knock-in mouse, and knock-down mouse, have been cultured, thus, paved a way to deepen our understanding of tumorigenesis, and provided a valuable system for the evaluation of cancer diagnosis, innovative therapeutic, and prevention. In this review paper, we highlight the biological characteristics of mouse, introduce spontaneous and inducible cancer mouse models and GEM models. In addition, some recent strategies and accomplishments for producing complicated cancer models in the mouse as well as the limitation of mouse model are discussed.