An update on the tools for creating transgenic animal models of human diseases – focus on atherosclerosis

Animal models of diseases are invaluable tools of modern medicine. More than forty years have passed since the first successful experiments and the spectrum of available models, as well as the list of methods for creating them, have expanded dramatically. The major step forward in creating specific disease models was the development of gene editing techniques, which allowed for targeted modification of the animal's genome. In this review, we discuss the available tools for creating transgenic animal models, such as transgenesis methods, recombinases, and nucleases, including zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and CRISPR/Cas9 systems. We then focus specifically on the models of atherosclerosis, especially mouse models that greatly contributed to improving our understanding of the disease pathogenesis and we outline their characteristics and limitations.疾病动物模型是现代医学不可或缺的宝贵工具。自首批成功实验开展至今已逾四十载，可获取的动物模型品类及其构建方法体系均得到了大幅拓展。构建特异性疾病模型的重大突破，当属基因编辑技术的发展——该技术可实现对动物基因组的靶向修饰。在本综述中，我们将探讨构建转基因动物模型的现有工具，包括转基因技术、重组酶以及核酸酶类工具，其中锌指核酸酶（zinc finger nuclease, ZFN）、转录激活因子样效应物核酸酶（transcription activator-like effector nuclease, TALEN）与CRISPR/Cas9系统均属此类。随后我们将聚焦动脉粥样硬化的动物模型，尤其是为深化该疾病发病机制研究作出重要贡献的小鼠模型，并概述其特性与局限性。