Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Int Rev Immunol. 2020;39(4):174-187. doi: 10.1080/08830185.2020.1742712. Epub 2020 Mar 23.
Laboratory animal models are beneficial when they recapitulate all or just some of the clinical and immunological manifestations of the disease. Various animals such as cats, rats, dogs, hamsters, guinea pigs, rabbits, horses, minks, pigs, and primates have been described lupus-like phenotype. However, a mouse has remained the preferable animal for scientific investigations as a result of their reduced lifespan, easy reproduction, markedly low costs, public acceptance, ease of genetic management, and the probability to stay under standardized conditions. It is highly challenging to establish a mouse model with all features of lupus because of the difficulty and the heterogeneity of the clinical features in systemic lupus erythematous (SLE). Additionally, due to the multiple differences between the mouse and human immune system, the direct translation usually fails. Each mouse model has specific characteristics and shares many subsets of aspects with the disease observed in humans, which gives researchers a tool to select their particular needs. Over 50 years, many mice models have been developed and used to dissect the pathogenesis of lupus, also to test novel drugs and therapies. In general, mice models that contribute considerably in SLE understanding can be divided into four groups: Spontaneous models, induced models, genetically modified models, along with humanizing mouse models that are the link between the mouse and human immune system. In this updated review, we will present what has been learned from different lupus mice models and how these models have contributed to a better understanding of lupus pathogenesis and treatment.
实验室动物模型在能够重现疾病的全部或部分临床和免疫学表现时是有益的。各种动物,如猫、鼠、狗、仓鼠、豚鼠、兔、马、貂、猪和灵长类动物,都已被描述为具有狼疮样表型。然而,由于其寿命较短、易于繁殖、成本明显较低、公众接受程度较高、遗传管理较为容易以及易于保持标准化条件,老鼠仍然是科学研究的首选动物。由于红斑狼疮(SLE)的临床特征存在难度和异质性,很难建立一种具有狼疮所有特征的老鼠模型。此外,由于老鼠和人类免疫系统之间存在多种差异,直接翻译通常会失败。每个老鼠模型都具有特定的特征,并与人类观察到的疾病有许多相似之处,这为研究人员提供了一种选择其特定需求的工具。50 多年来,已经开发并使用了许多老鼠模型来剖析狼疮的发病机制,还用于测试新的药物和疗法。一般来说,对 SLE 理解有重要贡献的老鼠模型可以分为四组:自发性模型、诱导性模型、基因修饰模型,以及连接老鼠和人类免疫系统的人源化老鼠模型。在本次更新的综述中,我们将介绍从不同狼疮老鼠模型中学到的知识,以及这些模型如何有助于更好地理解狼疮的发病机制和治疗方法。