Mouse models of lupus: what they tell us and what they don't.
Mouse models of lupus: what they tell us and what they don't.
复制标题
狼疮的鼠标：他们告诉我们什么，什么不告诉我们。
DOI：
10.1136/lupus-2016-000199
复制
发表时间：
2018
影响因子：
3.9
通讯作者：
Gilkeson G
中科院分区：
文献类型：
--
作者：
Richard ML;Gilkeson G
狼疮是一种复杂的异质性疾病，其特征是自身抗体产生和免疫复合物沉积，随后靶组织受损。人类疾病的动物模型是定义致病机制和测试新型治疗剂的宝贵工具。也许有比任何其他人类疾病更适用的狼疮小鼠模型。狼疮有自发模型、狼疮诱导模型、转基因诱导狼疮、基因敲除诱导狼疮和狼疮人源化小鼠模型。这些狼疮小鼠模型对我们对狼疮发病机制的了解做出了重大贡献，并作为新疗法概念验证的有价值的临床前模型。尽管具有实用性，狼疮小鼠模型也有其独特的局限性。尽管相似，但小鼠和人类的免疫系统不同，因此不能假设一种疾病的机制可以转化为另一种。化合物的功效和毒性在人类和小鼠之间可能存在显着差异，这也限制了直接翻译。最后，人类狼疮的异质性，无论是临床表现、潜在发病机制还是遗传学，在当前的小鼠模型中都没有完全体现。因此，在一种小鼠模型中证明一种治疗或疾病机制类似于在有限的人类狼疮亚群中证明一种机制/治疗。然而，这些限制并没有削弱动物模型的重要性，也没有削弱它们对我们了解狼疮所做出的重大贡献。
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.