Assay Development

ModiQuest Research offers custom assay development services fully tailored to the needs of our clients. In addition, we have developed a number of assays in-house, which we also offer on a fee-for-service basis (e.g. anti-TNF bioactivity assays, CAIA mouse model, etc.).

Below, you can find more information about our CAIA mouse model for Rheumatoid Arthritis applications.

Collagen Antibody Induced Arthritis (CAIA) mouse model for Rheumatoid Arthritis

Introduction

Collagen-induced arthritis (CIA) has been extensively used as a mouse-model for Rheumatoid Arthritis. However, it takes 3-5 weeks before the first signs of inflammation can be identified macroscopically. To shorten this time interval, ModiQuest Research has developed a rapid mouse model of Rheumatoid Arthritis: Collagen Antibody Induced Arthritis (CAIA). In the MQR-CAIA model, severe arthritis is induced by i.p. or i.v. injection of a mix of anti-collagen antibodies; the disease onset can be synchronized by LPS injection on day 3. The MQR-CAIA model is very efficient (100% incidence, depending on the mouse strain used), and ideal for the rapid screening of novel arthritis therapeutics and to study the mechanisms involved in the development of arthritis.

The CAIA antibodies can be delivered directly to clients for in-house animal model generation.Alternatively, complete animal studies are offered by ModiQuest Research.

Figure 1 DBA/ J1 mice were treated i.p. with MQR-CAIA mix (2.3 mg total). A control antibody (CTL) was used at the same concentration. LPS (25 ug/ mouse) was injected i.p. on day 7. Pictures are histological preparations of hind paws 25 days after anti-collagen antibody injection. SO Safranin-O staining (blue indicates bone, red indicates cartilage) HE Haematoxylin-Eosin staining.

* inflammatory infiltrate

Collagen-induced arthritis

Collagen-induced arthritis is an antibody mediated disease. Therefore, type II collagen specific antibodies can be used to induce arthritis in mice. ModiQuest Research’s mixture of type II collagen specific antibodies induces severe inflammation in the ankles and paws of DBA/ J1 mice (Figure 1), which resemble many aspects of arthritis. One of the biggest advantages of our monoclonal antibody-induced arthritis model is that arthritis is induced within 24-72 hours (Figure 2) instead of the four weeks required to induce arthritis after immunization with type II collagen. ModiQuest Research recommends highly susceptible DBA/ J1 mice. Other mouse strains may be used as well, however the amount of antibody cocktail required may vary.

Figure 2 CAIA using 8 monoclonal antibodies. Arthritis incidence (A) and total arthritis score (B) are indicated. Groups of 6 DBA/ J1 mice were treated i.p. with MQR-CAIA mix. Different concentrations of the antibody cocktail (0.8 mg, 2.4 mg, and 3.2 mg) were used. A control antibody (CTL) was used at a 2.3 mg concentration. LPS (25 μg/ mouse) was injected i.p. on day 7.

Unique features and advantages

  • Set of 8 thoroughly evaluated anti-collagen antibodies in one CAIA Cocktail Mix
  • LPS synchronization of inflammation onset simplifies treatment schedule
  • i.p. injection instead of i.v. injection
  • Easy and ready to use mouse model with high sensitivity
  • Incidence rates as high as 100%, which allows for a smaller size of animal groups
  • CAIA Cocktail Mix reduces the experimental time span
  • Ideal for rapid screening and evaluation of anti-inflammatory therapeutic agents

Figure 3 Effect of dexa-methasone and an anti-inflammatory antibody in a CAIA experiment. The therapeutic application of dexa-methasone in the CAIA model (applied daily from day 6 through 9) represses the inflammation for the duration of its administration. The mean arthritis score upon prophylactic administration of an anti-inflammatory antibody (on day 3, at the time of inflammation induction) shows a prolonged inflammation-repressing effect.

 

CAIA model to test anti-inflammatory agents for Rheumatoid Arthritis therapy

Dose specific efficacy of anti-inflammatory agents was demonstrated in the CAIA mouse model for Rheumatoid Arthritis. Three days following i.p. injection of the CAIA mix in DBA/ J1 mice, inflammation was induced and synchronized by LPS injection. In a typical efficacy experiment,the first signs of inflammation are observed on day 5 (Figure 3).

Animals receiving no anti-inflammatory agent developed maximum inflammation at day 9. A single prophylactic administration of an anti-inflammatory antibody (co-injected at the time of LPS induction) prevents the inflammatory response altogether. Daily administration of dexamethasone during the onset of inflammation temporarily represses the inflammation (administration from day 6, approximately halfway the maximum inflammatory response, through day 9, when the inflammation is fully repressed). Immediately after dexamethasone administration is lifted, inflammation is quickly restored at approximately half its maximum value. Prolonged daily administration of dexamethasone fully represses the inflammation (data not shown).

In conclusion

We have generated and validated a Collagen Antibody Induced Arthritis (CAIA) mouse model for Rheumatoid Arthritis. Using this CAIA model, the efficacy of anti-inflammatory agents can be tested upon prophylactic and therapeutic administration, within a time frame of three weeks.

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