TRANSGENIC MICE EXPRESSING HUMAN TUMOR-NECROSIS-FACTOR - A PREDICTIVE GENETIC MODEL OF ARTHRITIS
TRANSGENIC MICE EXPRESSING HUMAN TUMOR-NECROSIS-FACTOR - A PREDICTIVE GENETIC MODEL OF ARTHRITIS
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DOI：
10.1002/j.1460-2075.1991.tb04978.x
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发表时间：
1991-12-01
期刊：
影响因子：
11.4
通讯作者：
KOLLIAS, G
中科院分区：
文献类型：
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作者：
KEFFER, J;PROBERT, L;KOLLIAS, G
我们已经产生了携带和表达野生型和3 '-修饰的人肿瘤坏死因子（hTNF-α，恶病质）转基因的转基因小鼠品系。我们表明，可以在转基因小鼠中建立正确的、内毒素响应性的和巨噬细胞特异性的hTNF基因表达，并且我们提供的证据表明hTNF基因的3 '区域可能参与巨噬细胞特异性转录。携带3 '-修饰的hTNF转基因的转基因小鼠显示出表达失调的模式，并且有趣地发展为慢性炎性多关节炎。用抗人TNF的单克隆抗体治疗这些关节炎小鼠可完全防止这种疾病的发展。我们的研究结果表明，TNF直接参与关节炎的发病机制。转基因小鼠，可预见地发展关节炎代表了一种新的遗传模型，通过该模型，可以进一步研究这种疾病在人类中的发病机制和治疗。
We have generated transgenic mouse lines carrying and expressing wild-type and 3'-modified human tumour necrosis factor (hTNF-alpha, cachectin) transgenes. We show that correct, endotoxin-responsive and macrophage-specific hTNF gene expression can be established in transgenic mice and we present evidence that the 3'-region of the hTNF gene may be involved in macrophage-specific transcription. Transgenic mice carrying 3'-modified hTNF transgenes shows deregulated patterns of expression and interestingly develop chronic inflammatory polyarthritis. Treatment of these arthritic mice with a monoclonal antibody against human TNF completely prevents development of this disease. Our results indicate a direct involvement of TNF in the pathogenesis of arthritis. Transgenic mice which predictably develop arthritis represent a novel genetic model by which the pathogenesis and treatment of this disease in humans may be further investigated.