Model Description

Around week 6-8 mice start the gradual development of a milder form of arthritis than Tg197 also with 100% penetrance.  In contrast to the  short-living Tg197 mice, Tg3647 live more than one year having this pathology that closely resembles the chronicity and adult onset human rheumatoid arthritis and involves clinical symptoms that even reach  subluxation and dislocation of the front and hint limbs joints. This arthritis model offers the opportunity to test human therapeutics on established and advanced stages of rheumatoid arthritis.

Histology

Histopathology in the Tg3647 mice is characterized by infiltration of inflammatory cells, synovial hyperplasia, gradual articular cartilage destruction and bone erosion, resembling the chronic progression of human rheumatoid arthritis.

 
 

Figure 1: Representative histology images and graphs depicting the progression of arthritic pathology in Tg3647 animals.

Preclinical Efficacy Platform

Study design

Preclinical drug efficacy can be evaluated in a prophylactic regimen starting at 6 weeks of age upon disease initiation  or in a therapeutic regimen starting at any phase of the established disease. The duration of the studies is in either case a 5-week treatment period as the mice age normally (apart from the limb-restricted arthritis symptoms).

Figure 2: Tg3647 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
  • Histopathological  evaluation of the arthritis pathology in ankle joints


 

 

 

 

 

 

 

Figure 3: Representative graph of the in vivo progression of arthritic score in Tg3647 animals. Treatment with anti-hTNF therapeutics reverses disease symptoms.

Bibliography

1.  Zhang H, Hilton MJ, Anolik JH, Welle SL, Zhao C, Yao Z, Li X, Wang Z, Boyce BF and Xing L, 2014, "NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF-κB", J Clin Invest. 2014;124(7):3200-3214. doi:10.1172/JCI68901 (view article).