Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis

EMBO J. 1991 Dec;10(13):4025-31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Arthritis / genetics*
  • Arthritis / physiopathology
  • Blotting, Northern
  • Cartilage / pathology
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Joints / pathology
  • Mice
  • Mice, Transgenic
  • RNA / genetics
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • RNA