The TNF-α transgenic mouse model of inflammatory arthritis
The TNF-α transgenic mouse model of inflammatory arthritis
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DOI：
10.1007/s00281-003-0125-3
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发表时间：
2003-08-01
期刊：
影响因子：
--
通讯作者：
Schwarz, EM
中科院分区：
文献类型：
--
作者：
Li, P;Schwarz, EM
类风湿性关节炎是一种慢性炎症性疾病，影响多个周围关节。它是炎症性关节炎最常见的形式，其特征是滑膜增生、免疫细胞浸润、软骨破坏和骨侵蚀。为了深入了解该病的病因，已经建立了多种动物模型。12年前，George Kollias的实验室培育了一种转基因（Tg）小鼠，这种小鼠过度表达人类tnf - α，并产生了一种侵蚀性多发性关节炎，这种多发性关节炎具有在类风湿关节炎患者中观察到的许多特征。该小鼠模型的表型证实了tnf - α在类风湿关节炎的促炎级联反应中处于顶点的理论，并预示了抗tnf - α治疗的显著成功，这种治疗已经改变了这种疾病的有效管理。因此，TNF-Tg小鼠是解剖类风湿性关节炎致病过程的分子机制和评估新治疗策略疗效的非常有用的工具。在这篇综述中，我们(1)简要概述了tnf - α生物学及其在类风湿关节炎中的作用，(2)描述了各种TNF-Tg模型及其表型，(3)给出了该模型如何在实验中使用的例子。
Rheumatoid arthritis is a chronic inflammatory disorder that affects multiple peripheral joints. It is the most common form of inflammatory arthritis and is characterized by synovial hyperplasia, immune cell infiltration, cartilage destruction, and bone erosion. To gain insight into the etiology of the disease, a variety of animal models have been established. Twelve years ago George Kollias' laboratory generated a transgenic (Tg) mouse that over-expresses human TNF-alpha, and develops an erosive polyarthritis with many characteristics observed in rheumatoid arthritis patients. The phenotype of this mouse model validated the theory that TNF-alpha is at the apex of the pro-inflammatory cascade in rheumatoid arthritis, and foreshadowed the remarkable success of anti-TNF-alpha therapy that has transformed the effective management of this disease. As such, the TNF-Tg mice are very useful tools for dissecting the molecular mechanisms of the pathogenic process and evaluating the efficacy of novel therapeutic strategies for rheumatoid arthritis. In this review we (1) provide a brief summary of TNF-alpha biology and the role of this dominant cytokine in rheumatoid arthritis, (2) describe the various TNF-Tg models and their phenotypes, and (3) give examples of how this model has been used experimentally.