Fan Jianglin, Wang Yanli, Chen Y Eugene
Department of Pathology, Xi'an Medical University, Xi'an, China.
Department of Molecular Pathology, Faculty of Medicine, Graduate School of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan.
Front Genet. 2021 Feb 2;12:614379. doi: 10.3389/fgene.2021.614379. eCollection 2021.
Rabbits are one of the most used experimental animals for investigating the mechanisms of human cardiovascular disease and lipid metabolism because they are phylogenetically closer to human than rodents (mice and rats). Cholesterol-fed wild-type rabbits were first used to study human atherosclerosis more than 100 years ago and are still playing an important role in cardiovascular research. Furthermore, transgenic rabbits generated by pronuclear microinjection provided another means to investigate many gene functions associated with human disease. Because of the lack of both rabbit embryonic stem cells and the genome information, for a long time, it has been a dream for scientists to obtain knockout rabbits generated by homologous recombination-based genomic manipulation as in mice. This obstacle has greatly hampered using genetically modified rabbits to disclose the molecular mechanisms of many human diseases. The advent of genome editing technologies has dramatically extended the applications of experimental animals including rabbits. In this review, we will update genetically modified rabbits, including transgenic, knock-out, and knock-in rabbits during the past decades regarding their use in cardiovascular research and point out the perspectives in future.
兔子是研究人类心血管疾病机制和脂质代谢最常用的实验动物之一，因为在系统发育上它们比啮齿动物（小鼠和大鼠）更接近人类。100多年前，用高胆固醇饲料喂养的野生型兔子首次被用于研究人类动脉粥样硬化，并且至今仍在心血管研究中发挥着重要作用。此外，通过原核显微注射产生的转基因兔子为研究许多与人类疾病相关的基因功能提供了另一种手段。由于缺乏兔子胚胎干细胞和基因组信息，长期以来，科学家们一直梦想着像在小鼠中那样，通过基于同源重组的基因组操作获得基因敲除兔子。这一障碍极大地阻碍了利用基因工程改造的兔子来揭示许多人类疾病的分子机制。基因组编辑技术的出现极大地扩展了包括兔子在内的实验动物的应用。在这篇综述中，我们将更新过去几十年里基因工程改造的兔子，包括转基因兔、基因敲除兔和基因敲入兔在心血管研究中的应用情况，并指出未来的发展前景。
