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Ann Rheum Dis. Jul 2005; 64(7): 981–987.
Published online Jan 7, 2005. doi:  10.1136/ard.2004.029710
PMCID: PMC1755557

A longitudinal study on an autoimmune murine model of ankylosing spondylitis

Abstract

Background: Proteoglycan aggrecan (PG)-induced arthritis (PGIA) is the only systemic autoimmune murine model which affects the axial skeleton, but no studies have been performed characterising the progression of spine involvement.

Objectives: To follow pathological events in experimental spondylitis, and underline its clinical, radiographic, and histological similarities to human ankylosing spondylitis (AS); and to determine whether the spondyloarthropathy is a shared phenomenon with PGIA, or an "independent" disease.

Methods: Arthritis/spondylitis susceptible BALB/c and resistant DBA/2 mice, and their F1 and F2 hybrids were immunised with cartilage PG, and radiographic and histological studies were performed before onset and weekly during the progression of spondylitis.

Results: About 70% of the PG immunised BALB/c mice develop spondyloarthropathy (proteoglycan-induced spondylitis (PGISp), and the progression of the disease is very similar to human AS. It begins with inflammation in the sacroiliac joints and with enthesitis, and then progresses upwards, affecting multiple intervertebral disks. In F2 hybrids of arthritis/spondylitis susceptible BALB/c and resistant DBA/2 mice the incidence of arthritis was 43.5%, whereas the incidence of spondylitis was >60%. Some arthritic F2 hybrid mice had no spondylitis, whereas others developed spondylitis in the absence of peripheral arthritis.

Conclusions: The PGISp model provides a valuable tool for studying autoimmune reactions in spondylitis, and identifying genetic loci associated with spondyloarthropathy.

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Selected References

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Figures and Tables

Figure 1
 Time course of immunisation, number of animals killed and analysed weekly, and the time of onset of arthritis in peripheral joints (PGIA; thick black arrow) and spondylitis (PGISp; thick white arrow). A total of 210 female BALB/c mice were immunised ...
Figure 2
 Inflammation of the sacroiliac joints and progression of ankylosis in PG immunised BALB/c mice with spondylitis. The normal sacroiliac joint (A), which is first eroded by a synovial pannus-like hyperproliferative tissue (black arrows) at the ...
Figure 3
 Cervical spine segments in (A, B, C) normal mice and in (D, E, F) mice afflicted with spondylitis. The affected disks are shown with the ankylosing osteophytes (black arrows: IVD C4/C5), which protrude and compress the spinal cord (SpC) (D). ...
Figure 4
 Progression of spondylitis in the lumbar spine (L3-5) in PG immunised BALB/c mice. Alizarin red stains bone red, while alcian blue stains the cartilaginous structures blue. Black arrowheads indicate the cartilaginous growth plates of the vertebral ...
Figure 5
 (A) Analysis and comparison of PG-induced arthritis (PGIA: A) and PG-induced spondylitis (PGISp: Sp) in 81 BALB/c (B/c), 48 DBA/2 (D/2) mice and their F1 and F2 hybrids (BALB/c x DBA/2) immunised with human cartilage PG. All mice were injected ...

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