Type II Collagen-Induced Arthritis (CIA) (mouse)

Description

The type II collagen-induced arthritis (CIA) model is one of the most widely studied and utilized models of arthritis as it shares immunological and pathological features with human rheumatoid arthritis (RA). Disease is induced in genetically susceptible rodents by immunization with chicken type II collagen emulsified in complete Freund’s adjuvant (CFA), followed by an additional immunization with chicken type II collagen emulsified in incomplete Freund’s adjuvant (IFA). After the second injection, LPS is given to synchronize the onset of arthritis. This paradigm results in inflammation of the paws which is evaluated over the course of the study using an established scoring scale, in addition to monitoring paw edema through caliper measurement. The immunopathogenesis of CIA involves both T and B cell-specific responses to type II collagen. Corticosteroids and biologics are effective in treating disease and can be used as positive comparator arms.

  • Advantages: Mimics important features of human RA, antigen-specific T and B cells present.
  • Disadvantage: Longer study time due to induction approach.
Model Systems
  • DBA/1 (predominant strain)
  • Rats (Sprague Dawley, Wistar, Lewis)
Standard Readouts
  • Percent weight change
  • Clinical arthritis assessment
  • Paw edema
  • Terminal histopathology and/or IHC analyses
Additional Readouts
  • Localized and systemic cytokine
  • Peripheral lymphoid organ immunophenotyping (Flow Cytometry)
  • Gene expression
  • Custom assays
Representative DataClick Image to Enlarge
Percent Weight Change in CIA mouse model

Animals are weighed daily, and body weight changes as compared to Day 0 are calculated. The AUC is calculated to compare treatment arms and is shown in the inset. (****p<0.001)

Clinical Arthritis Scoring in CIA Mouse Model

Mice with CIA are assessed three times per week for clinical arthritis development. Each paw is scored on a scale of 0-4, and the sum score is shown. The AUC is calculated to compare treatment arms and is shown in the inset. (*p<0.05; **p<0.01)

Paw Edema Assessment in CIA Mouse Model

Paw swelling/edema is assessed weekly in the mouse CIA model by measurement with a digital caliper. Each paw is measured, and the average is presented for each animal.

Daniel Lichtman

Managing Partner