Model Description

Tg197hTNFR1KI mice develop spontaneous arthritis characterized by swelling of the ankles, hind limb distortion and impaired movement, closely resembling the human pathology. Symptoms such as joint swelling start to develop from 6 weeks of age and the disease gradually develops to fully established pathology including ankylosis  and severely impaired movement by 12-15 weeks of age.

Histology

Histopathology in Tg197hTNFR1KI mice is characterized by infiltration of inflammatory cells, synovial hyperplasia, articular cartilage destruction and bone erosion symptoms, closely resembling those of human rheumatoid arthritis.

  

Figure 1: Representative histology images of A: wild type and B: Tg197hTNFR1KI animals at 12 weeks of age depicting the symptoms of Infiltration of inflammatory cells, Synovial hyperplasia, Articular cartilage destruction and Bone erosions evident as Tg197 arthritic pathology.

Preclinical Efficacy evaluation

Study design

Preclinical drug efficacy is evaluated  either in a prophylactic regimen starting dose administration at 3 weeks of age prior to disease initiation and lasting for 9 weeks (12 weeks of age) or a therapeutic regimen starting dose administration at 6 weeks of age upon disease initiation and lasting for 9 weeks (15 weeks of age).


Figure 2: Tg197hTNFR1KI animals can be treated using either a prophylactic or a therapeutic 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 3: Representative graphs of the progression of the in vivo arthritic score in Tg197hTNFR1KI animals observed at 13 weeks of age. Therapeutic treatment with commercially available anti-hTNF or anti-hTNFR1 therapeutics reverses the disease symptoms.