Model Description

TgA86 mice overexpress mouse transmembraneTNF from a Δ1-12 mTNF-globin transgene. They develop with 100% incidence peripheral and axial joint pathology accompanied by new bone formation features, all characteristic of human SpA pathology.  

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Figure 1: Representative images of hind limbs of wt (left) and TgA86 (right) mice depicting  peripheral pathology in TgA86 animals.
 

Histology

Histopathology of TgA86 peripherla joints is characterized by synovial hyperplasia, articular cartilage destruction, bone erosion and ectopic cartilage formation while  tail vertebrae  display signs of bone marrow oedema and intravertebral disc degeneration. Together these features closely resemble those of human spondyloarthropathies.

  

Figure 2: Representative TgA86 histology images of A: Toluidine blue stained tail vertebrae and B: Safranin O stained ankle joints, depicting at 10 weeks of age inflammatory infiltration, synovial hyperplasia, articular cartilage destruction and bone erosions.

 

Preclinical Efficacy evaluation

Study design

Preclinical drug efficacy is evaluated either with an early or with a late treatment starting at 3 or 9 weeks of age respectively.

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 tail bending and ankylosis for the whole duration of the study
  • Histopathological  evaluation of the  pathology in ankle joints and tail vertebrae
  • µCT analysis

Figure 3: Representative graphs of the progression of the in vivo arthritic score (left panel) and the tail pathology  score (right panel) in TgA86 animals. Treatment with etanercept ameliorates the disease symptoms.

Bibliography

1. Alexopoulou L, Pasparakis M, Kollias G., 1997, "A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF receptor signaling", Eur J Immunol, 27(10):2588-92. (view article)

2. Vieira-Sousa E, van Duivenvoorde LM, Fonseca JE, Lories RJ, Baeten DL. 2015 “Review: animal models as a tool to dissect pivotal pathways driving spondyloarthritis” , Arthritis Rheumatol. 67, 2813-27. (view article) (view article)
Biomedcode's disease models are highlighted in a new review discussing animal models of spondyloarthritis.