Tg197 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 start to develop at 3-4 weeks of age with established arthritis at 6-7 weeks of age and fully exacerbated pathology by 10 weeks of age.
Histopathology in Tg197 mice is characterized by infiltration of inflammatory cells, synovial hyperplasia, articular cartilage destruction and bone erosion symptoms, closely resembling those of human rheumatoid arthritis.
Preclinical Efficacy evaluation
Preclinical drug efficacy can be evaluated either in a:
> prophylactic regimen starting at 3 weeks of age upon disease initiation and lasting for 7 weeks up to the 10th week of age of the animals. Ideal for the evaluation of therapeutics in peventing the development of disease symptoms.
> therapeutic regimen starting at 6 weeks of age when the disease is fully established and lasting for 6 weeks up to the 12th week of age of the animals. Ideal for the evaluation of therapeutics in reversing disease symptoms.
- 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
The article describes the generation and phenotypic characterization of Tg197 model of arthritis.
3. A published abstract by Abgenix Biopharma using Tg197 and Tg5453 for testing their antibodies (view abstract).
The article describes the generation and phenotype of the TgK21 mice, a model of multiple sclerosis caused by human TNF.
4. Shealy DJ, Wooley PH, Emmell E, Volk A, Rosenberg A, Treacy G, Wagner CL, Mayton L, Griswold DE, Song XY. 2002, “Anti-TNF-alpha antibody allows healing of joint damage in polyarthritic transgenic mice”. Arthritis Res. 4(5):R7. (view article).
A recent review that highlights the instrumental role of the Tg197 model of arthritis in providing the proof of concept for the anti-TNF therapy for the efficient treatment of arthritis.