Collagen induced arthritis (CIA) in mice


Figure 1: Clinical symptoms of CIA in mice.

A: Forepaw of a mouse with CIA (left side/right paw). Symptoms of CIA are i.a. swelling and redness of peripheral joints.

B: Clinical score after CIA onset.

Species

Mouse

Fields of application

Collagen induced arthritis (CIA) in mice is a well characterized animal model for rheumatoid arthritis (RA) in man. CIA is induced by intradermal injection of an emulsion consisting of collagen II and an adjuvant into the tail base. Within some days animals develop arthritic symptoms in the limbs. CIA is an acute model for RA. About 35 days after onset clinical symptoms decline. Assessment of clinical symptoms is realized by means of an established scoring system.

  • Pharmacodynamics and pharmacokinetics
  • (Patho)physiological processes
  • Therapeutic efficacy
  • Proof of concept

Endpoints/Outcome parameter

  • Score (severity of symptoms; in vivo)
  • Immune cells in full blood (in vivo)
  • Cytokines and RA marker protein levels in blood plasma (in vivo)
  • Swelling, destruction, pannus formation, immune cell infiltration (ex vivo)
  • Halogenating activity of myeloperoxidase (MPO; in vivo)

Readout parameter

  • Scoring
  • Flow cytometry
  • ELISA/CBA (cytometric bead array)
  • RT-PCR
  • Western Blot
  • Histology (various classical histological stains)
  • Immunohistochemistry
  • MPO activity assay

Quality management and validation

  • Controls
  • Blinded induction
  • Blinded data collection and analysis
  • Randomisation
  • Allocation concealment
  • Biometric Expertise
  • Internal quality management

References

  • Cooperation project with Nuvo Research GmbH (Leipzig): „Die Entwicklung des Wirkstoffes WF10 zu einer innovativen Arzneimittel-Plattform zur Therapie chronisch inflammatorischer Erkrankungen“

  • Lange F, Bajtner E, Rintisch C, Nandakumar KS, Sack U, Holmdahl R. Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis. Ann Rheum Dis. 2005; 64(4):599-605.

  • Leichsenring A, Sack U, Lange F, Isensee T, Guntermann H. Anti-inflammatory effects of WF10 in a mouse model of rheumatoid arthritis. J. Immunol. 2013; 190, 68.20.

  • Flemmig J, Schwarz P, Bäcker I, Leichsenring A, Lange F, Arnhold J. Rapid and reliable determination of the halogenating peroxidase activity in blood samples. J Immunol Methods. 2014; 415:46-56