Institute of Cardiovascular Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing, China.
Methods Mol Biol. 2022;2419:433-459. doi: 10.1007/978-1-0716-1924-7_26.
Animal models of human diseases play an extremely important role in biomedical research. Among them, mice are widely used animal models for translational research, especially because of ease of generation of genetically engineered mice. However, because of the great differences in biology between mice and humans, translation of findings to humans remains a major issue. Therefore, the exploration of models with biological and metabolic characteristics closer to those of humans has never stopped.Although pig and nonhuman primates are biologically similar to humans, their genetic engineering is technically difficult, the cost of breeding is high, and the experimental time is long. As a result, the application of these species as model animals, especially genetically engineered model animals, in biomedical research is greatly limited.In terms of lipid metabolism and cardiovascular diseases, hamsters have several characteristics different from rats and mice, but similar to those in humans. The hamster is therefore an ideal animal model for studying lipid metabolism and cardiovascular disease because of its small size and short reproduction period. However, the phenomenon of zygote division, which was unexpectedly blocked during the manipulation of hamster embryos for some unknown reasons, had plagued researchers for decades and no genetically engineered hamsters have therefore been generated as animal models of human diseases for a long time. After solving the problem of in vitro development of hamster zygotes, we successfully prepared enhanced green fluorescent protein (eGFP) transgenic hamsters by microinjection of lentiviral vectors into the zona pellucida space of zygotes. On this basis, we started the development of cardiovascular disease models using the hamster embryo culture system combined with the novel genome editing technique of clustered regularly interspaced short palindromic repeats (CRISPR )/CRISPR associated protein 9 (Cas9). In this chapter, we will introduce some of the genetically engineered hamster models with dyslipidemia and the corresponding characteristics of these models. We hope that the genetically engineered hamster models can be further recognized and complement other genetically engineered animal models such as mice, rats, and rabbits. This will lead to new avenues and pathways for the study of lipid metabolism and its related diseases.
动物疾病模型在生物医学研究中起着极其重要的作用。其中,小鼠是广泛应用于转化研究的动物模型,特别是因为易于生成基因工程小鼠。然而,由于小鼠和人类之间存在巨大的生物学差异,将研究结果转化为人类仍然是一个主要问题。因此,探索具有更接近人类生物学和代谢特征的模型从未停止过。
虽然猪和非人类灵长类动物在生物学上与人类相似,但它们的基因工程在技术上具有难度,繁殖成本高,实验时间长。因此,这些物种作为模型动物,特别是基因工程模型动物,在生物医学研究中的应用受到了极大的限制。
在脂质代谢和心血管疾病方面,仓鼠具有与大鼠和小鼠不同但与人类相似的几个特征。因此,仓鼠是研究脂质代谢和心血管疾病的理想动物模型,因为它的体型小,繁殖周期短。然而,仓鼠胚胎操作中由于某些未知原因导致合子分裂现象意外受阻,这一现象困扰了研究人员数十年,因此很长一段时间内都没有产生基因工程仓鼠作为人类疾病的动物模型。在解决仓鼠合子体外发育问题后,我们成功地通过将慢病毒载体注射到合子的透明带空间中,制备了增强型绿色荧光蛋白(eGFP)转基因仓鼠。在此基础上,我们开始利用仓鼠胚胎培养系统结合新型基因组编辑技术 CRISPR/Cas9 开发心血管疾病模型。在本章中,我们将介绍一些具有血脂异常的基因工程仓鼠模型及其模型的相应特征。我们希望基因工程仓鼠模型能够得到进一步的认可,并补充其他基因工程动物模型,如小鼠、大鼠和兔子。这将为脂质代谢及其相关疾病的研究开辟新的途径和思路。