Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis
| Autor: | Lesley Probert, J. Keffer, E. Kaslaris, Spiros Georgopoulos, D. Kioussis, H. Cazlaris, George Kollias |
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| Rok vydání: | 1991 |
| Předmět: |
Genetically modified mouse
Transgene Arthritis Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Pathogenesis Mice Gene expression Genetic model medicine Animals Humans Molecular Biology Regulation of gene expression General Immunology and Microbiology Tumor Necrosis Factor-alpha General Neuroscience Antibodies Monoclonal Blotting Northern medicine.disease Disease Models Animal Cartilage Gene Expression Regulation Immunology RNA Joints Tumor necrosis factor alpha Research Article |
| Zdroj: | The EMBO Journal. 10:4025-4031 |
| ISSN: | 0261-4189 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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