Model Description

Tg5453 mice develop spontaneous arthritis characterized by swelling of the ankles, hind limb distortion, impaired movement and progressive weight loss, closely resembling the human pathology. Symptoms such as joint swelling start to develop from 2 weeks of age and the disease rapidly develops to fully exacerbated pathology by 7 weeks of age including ankylosis, severely impaired movement and cachexia.

Figure 1: Representative image depicting in vivo arthritis in Tg5453 animal.


Histology

Histopathology in the Tg5453 mice is characterized by infiltration of inflammatory cells, synovial hyperplasia, articular cartilage destruction and bone erosion, closely resembling that of human rheumatoid arthritis.

  

Figure 2: Representative histology images of A: wild type and B: Tg197 animals at 7 weeks of age depicting the symptoms of Infiltration of inflammatory cells, Synovial hyperplasia, Articular cartilage destruction and Bone erosions evident as Tg5453 arthritic pathology.

Preclinical efficacy evaluation

Study design

Preclinical drug efficacy is evaluated in a prophylactic regimen starting dose administration at 2 weeks of age upon disease initiation and lasting for 5 weeks up to the 7th week of age of the animals. 


Figure 3: Tg5453 animals can be treated using a prophylactic regimen.
 

Read-out parameters

  • In vivo body weight measurements for the whole duration of the study
  • In vivo evaluation of ankle and paw  joint swelling for the whole duration of the study
  • In vivo evaluation of the progression of arthritis as depicted in the general well being of the animals & the development of cachexia
  • Histopathological  evaluation of the arthritis pathology in ankle joints

Figure 4: Representative graphs of the progression of the in vivo arthritic score in Tg5453 animals (left panel) and the histopathological arthritic score (right panel) observed at 7 weeks of age. Prophylactic treatment with commercially available anti-hTNF therapeutics prevents the development of disease symptoms.

Bibliography

1. Georgopoulos S., Plows D., Kollias G., 1996, "Transmembrane TNF is sufficient to induce localized tissue toxicity andchronic inflammatory arthritis in transgenic mice", J. Inflamm., 46, 86-97. (view article).
The article describes the generation and phenotypic characterization of Tg5453 model of arthritis.