Gorshkova E A, Zvartsev R V, Drutskaya M S, Gubernatorova E O
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Immunology Department, Biological Faculty, Moscow State University, Moscow, 119234 Russia.
Mol Biol (Mosk). 2019 Sep-Oct;53(5):755-773. doi: 10.1134/S0026898419050070.
Dysregulated proinflammatory cytokine expression may result in the development of severe pathologies, such as rheumatoid arthritis, psoriasis, and neurodegenerative diseases. Transgenic mice and, in particular, those with controllable systemic overexpression of proinflammatory cytokines have recently become an essential instrument to study the molecular mechanisms underlying disease development. Importantly, many of the models are humanized by introducing a human cytokine gene, while leaving or removing the respective endogenous mouse gene. Humanized mice are especially valuable for biomedical research as they provide a relevant model to develop therapies based on blocking the pathogenic activity of a cytokine or to establish the functional significance of genome polymorphisms. The review discusses the available humanized mouse models with overexpression of key proinflammatory cytokines (TNF, IL-ip, and IL-6) and inflammatory cytokines with more specific functions (IL-8, IL-17, and IL-32) and their significance for basic and clinical research.
促炎细胞因子表达失调可能导致严重病症的发生,如类风湿性关节炎、银屑病和神经退行性疾病。转基因小鼠,尤其是那些能够可控地全身过表达促炎细胞因子的小鼠,最近已成为研究疾病发生分子机制的重要工具。重要的是,许多模型通过引入人类细胞因子基因同时保留或去除相应的内源性小鼠基因而实现人源化。人源化小鼠对生物医学研究特别有价值,因为它们为基于阻断细胞因子致病活性开发疗法或确定基因组多态性的功能意义提供了相关模型。本文综述了关键促炎细胞因子(TNF、IL-1β和IL-6)以及具有更特定功能的炎性细胞因子(IL-8、IL-17和IL-32)过表达的现有人类化小鼠模型及其在基础和临床研究中的意义。