Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis.
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.
Keffer
J
J
Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece.
Probert
L
L
Cazlaris
H
H
Georgopoulos
S
S
Kaslaris
E
E
Kioussis
D
D
Kollias
G
G
D000818:Animals; D000911:Antibodies, Monoclonal; D001168:Arthritis / Q000235:genetics* / Q000503:physiopathology; D015152:Blotting, Northern; D002356:Cartilage / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007596:Joints / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D012313:RNA / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000502:physiology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D012313:RNA