Richard Mara Lennard, Gilkeson Gary
Medical University of South Carolina, Charleston, South Carolina, USA.
Lupus Sci Med. 2018 Jan 21;5(1):e000199. doi: 10.1136/lupus-2016-000199. eCollection 2018.
Lupus is a complex heterogeneous disease characterised by autoantibody production and immune complex deposition followed by damage to target tissues. Animal models of human diseases are an invaluable tool for defining pathogenic mechanisms and testing of novel therapeutic agents. There are perhaps more applicable murine models of lupus than any other human disease. There are spontaneous models of lupus, inducible models of lupus, transgenic-induced lupus, gene knockout induced lupus and humanised mouse models of lupus. These mouse models of lupus have contributed significantly to our knowledge of the pathogenesis of lupus and served as valuable preclinical models for proof of concept for new therapies. Despite their utility, mouse models of lupus have their distinct limitations. Although similar, mouse and human immune systems are different and thus one cannot assume a mechanism for disease in one is translatable to the other. Efficacy and toxicity of compounds can vary significantly between humans and mice, also limiting direct translation. Finally, the heterogeneous aspects of human lupus, both in clinical presentation, underlying pathogenesis and genetics, are not completely represented in current mouse models. Thus, proving a therapy or mechanism of disease in one mouse model is similar to proving a mechanism/therapy in a limited subset of human lupus. These limitations, however, do not marginalise the importance of animal models nor the significant contributions they have made to our understanding of lupus.
狼疮是一种复杂的异质性疾病，其特征为自身抗体产生和免疫复合物沉积，随后导致靶组织损伤。人类疾病的动物模型是确定致病机制和测试新型治疗药物的宝贵工具。与任何其他人类疾病相比，可能有更多适用的狼疮小鼠模型。有狼疮自发模型、狼疮诱导模型、转基因诱导的狼疮、基因敲除诱导的狼疮以及狼疮人源化小鼠模型。这些狼疮小鼠模型极大地增进了我们对狼疮发病机制的了解，并作为有价值的临床前模型用于新疗法的概念验证。尽管它们很有用，但狼疮小鼠模型有其明显的局限性。虽然小鼠和人类免疫系统相似，但并不相同，因此不能假定一种疾病在一种动物中的机制可直接套用到另一种动物。化合物在人类和小鼠中的疗效和毒性可能有显著差异，这也限制了直接套用。最后，人类狼疮在临床表现、潜在发病机制和遗传学方面的异质性，在当前的小鼠模型中并未得到完全体现。因此，在一种小鼠模型中证明一种疗法或疾病机制，类似于在人类狼疮的一个有限子集中证明一种机制/疗法。然而，这些局限性并没有削弱动物模型的重要性，也没有削弱它们对我们理解狼疮所做出的重大贡献。
