Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that is widely used to address questions of disease pathogenesis and to validate therapeutic targets. Collagen-induced arthritis models can be performed in both in mice or rats by immunization with heterologous type II collagen in adjuvant. Susceptibility to collagen-induced arthritis is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T-cell and B-cell response to type II collagen.
Pathological Features:
The chief pathological features of collagen-induced arthritis include a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, pannus formation, cartilage degradation, erosion of bone, and fibrosis. As in human rheumatoid arthritis, pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-a), interleukin-1b (IL-1b) and IL-6 are increased in collagen-induced arthritis. Biological therapies designed to interfere with these mediators are active in these models.
Measurements:
Disease activity is assessed by measuring swelling in the affected joints (paw volume or thickness) over time. Treatments can be assessed in either prophylactic or therapeutic testing paradigms. Additional measure of disease activity include evaluation of serum IL-1b, IL-6, C-reactive protein (CRP) or serum amyloid A (SAA), and erythrocyte sedimentation rate. Bone lesion scoring conducted by preclinical Positron Emission Tomography (preclinical PET). MIR typically measures all four paws for thickness and gives an average paw thickness for each animal at each timepoint. Animal body weights are typically taken 2 times per week.
General Outline of Study:
Collagen-induced arthritis can be induced in either rats or mice using bovine type II collagen. Prophylactic studies in rats are carried out over 28 days (50 days for mice), while therapeutic studies require a 14 day protocol (26 for mice).
Histology and Analytical Services :
MIR Preclinical Services has established strategic partners for histology, immunohistochemistry, Phamacokinetics, blood chemistries and other pertainent services that clients may request. Each strategic partner is a specialist in the area of interest and MIR Preclinical Services can offer these services as a part of its offerings.
Reports:
Each week clients receive an interim report that contains all the data for a current study up to that day. This contains data on body weights, changes in body weights over time, paw measurements, changes in paw measurements over time, clinical based scoring, daily census, comments, necropsy findings and summary graphics. Clients will also receive an email detailing each significant study milestone including when animals are ordered, when animals are injected with inflammatory agents, when treatment begins, when treatment ends and when the study ends. Final reports contain detail materials and methods, statistical analysis, publication quality tables and figures, popular enpoint calculations (paw thickness, peak swelling, time to peak swelling, clinical grade scoring, overall severity, AUC, etc.)and all raw data for the study. Custom endpoints and analyses can also be generated upon request. MIR Preclinical Services strives to have final reports to clients within 3 weeks of the euthanasia of the last animal on study for preclinical pharmacology experiments and between 5 to 7 weeks for extensive preclinical imaging studies (depending on size and imaging modality).
Imaging in Rat Collagen-Induced Arthritis :
MIR Preclinical Services is the leading contract research organization in the application of preclinical imaging to preclinical models of cancer and arthritis. MIR has preclinical computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and biophotonic imaging capabilities. MIR Preclinical Services owns all of their own imaging equipment and operates this equipment on site. All of the company's imaging equipment is state-of-the-art and designed exclusively for small animals.
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