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Rheumatoid arthritis (RA) animal model

Rheumatoid arthritis (RA) animal model

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Rheumatoid arthritis
Endocrine and Immune system models

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Model Introduction

Model Introduction

Platform Service Advantages

Platform Service Advantages

Experimental results

Experimental results

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Rheumatoid arthritis

Introduction to RA Animal Models

Rheumatoid arthritis is a chronic, inflammatory, systemic autoimmune disease. Its hallmark pathological feature is synovitis: during the acute phase, the synovium becomes swollen and exhibits exudation with neutrophil infiltration; in the chronic phase, the synovium undergoes hyperplasia and thickening, leading to the formation of pannus. The pannus is the pathological basis for joint destruction, deformity, and functional impairment, ultimately driving the disease into an irreversible stage.

Service Advantages of Aniphe BioLab’s RA Animal Model Platform

This platform is capable of establishing a variety of rheumatoid arthritis models, with mature technologies and stringent quality control, providing comprehensive support for related experimental studies and drug development.

Comprehensive model coverage

A full range of modeling methods is available.

Mainstream methods such as collagen induction and adjuvant induction can be employed to suit different experimental requirements.

Standardization of the modeling process

Model phenotype stability

Typical pathological features such as joint swelling and inflammation are observed, with a high modeling success rate and minimal intergroup variability.

Multidimensional Evaluation System

Standardized Process Management

Standardized procedures and husbandry throughout the entire process, with regular monitoring of joint condition and traceable data.

Adapted for multi-cycle studies

Comprehensive testing and refinement

A variety of tests can be performed, including joint scoring, imaging studies, histopathology, and inflammatory cytokine assays.

Standardization of Data Delivery

The experimental protocol is flexible.

The modeling duration and dosing schedule can be adjusted to accommodate various intervention experimental designs.

Standardization of Data Delivery

One-stop closed-loop service

The entire process, from model establishment and observation to biomarker assessment, is conducted independently, seamlessly integrating basic research with preclinical regulatory submissions.

Modeling cycle

3-4 weeks

1  Laboratory animals

DBA/1 male mouse

1  Positive drug

Methotrexate may be selected: a dihydrofolate reductase inhibitor that exerts anti-inflammatory and immunomodulatory effects by inhibiting the synthesis of purines and pyrimidines, making it a first-line therapeutic agent for RA; alternatively, etanercept—a TNF-α antagonist—may be chosen, which can significantly reduce joint inflammation and bone erosion.

1  Application areas

This model is employed to investigate the immune dysregulation, synovial damage, and bone destruction underlying rheumatoid arthritis, enabling the screening of anti-inflammatory, immunomodulatory, and joint‑function‑improving agents, as well as the evaluation of their efficacy and safety. It can also be utilized for target validation and the development of natural products and innovative therapeutics, making it suitable for both basic research and preclinical programs such as IND submissions.

Experimental results

Collagen-induced CIA model:

Modeling procedure:

1. Acclimatization period (Weeks −1 to 0): Following purchase, mice are housed on standard maintenance chow and acclimated for one week.

2. Primary immunization (Week 0): Do not change the diet. Emulsify bovine type II collagen with an equal volume of complete Freund’s adjuvant (CFA) to form a stable emulsion, and inject it intradermally at the base of the mouse tail. Slowly administer 50 μL per mouse; upon completion of the injection, promptly withdraw the needle and gently pinch the injection site for 3 minutes to prevent leakage of the emulsion.

3. Secondary (booster) immunization (2 weeks): Twenty-one days after the primary immunization, administer a booster dose by thoroughly emulsifying bovine type II collagen with an equal volume of incomplete Freund’s adjuvant (IFA). The injection technique is the same as for the primary immunization.

4. Acute phase (3–4 weeks): 7–14 days after booster immunization, arthritis symptoms begin to appear, with inflammation predominantly affecting the ankle joints and foot digits.

5. Pharmacological efficacy trial period: Administration may commence at the time of the primary immunization, prior to the secondary immunization, or after disease onset; the specific timing should be determined based on the study’s research objectives.

6. Monitoring during the study: Weekly body weight measurements and joint swelling scoring will be performed.

References:

01 Williams, R.O. (2007). Collagen-Induced Arthritis in Mice. In: Sioud, M. (eds) Target Discovery and Validation Reviews and Protocols. Methods in Molecular Biology™, vol 361. Humana Press. https://doi.org/10.1385/1-59745-208-4:265.

02 Grötsch, B., Bozec, A., Schett, G. (2025). Models of Rheumatoid Arthritis. In: Idris, A.I. (eds) Bone Research Protocols. Methods in Molecular Biology, vol 2885. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-4306-8_18.

03 Webb, D.R. (2018). Animal Models of Rheumatoid Arthritis. In: Ragab, G., Atkinson, T., Stoll, M. (eds) The Microbiome in Rheumatic Diseases and Infection. Springer, Cham. https://doi.org/10.1007/978-3-319-79026-8_6

Key milestone photos

Emulsions require thorough emulsification, but excessive emulsification should be avoided to prevent clogging the syringe. On ice, homogenize and emulsify for 20 minutes; the resulting product should resemble whipped cream and remain intact when dropped into water.

 

 

Compared with the control group mice, the model mice generated using this modeling method exhibited severe swelling of the paw pads and joints.

 

 

Weight monitoring curve

Following the first immunization, both the control and model groups exhibited a steady increase in body weight, with the model group showing a slightly lower gain than the control group. After the booster immunization, the model group’s body weight demonstrated a decreasing trend over time.

 

 

Joint Swelling Score

A 0–4 scoring system was used to assess the degree of joint swelling and erythema in each footpad:

0 points: Normal, no redness or swelling

1 point: Mild erythema and edema, localized to the toes or ankle joint.

2 points: Moderate erythema and edema, involving the entire footpad.

3 points: Severe erythema and edema, extending to the entire foot below the ankle joint.

4 points: Severe erythema and swelling accompanied by joint deformity or ankylosis.

 

 

Throughout the experiment, joint swelling scores were assessed in mice. Following the initial immunization, the model group exhibited a slight increase in scores over time, generally ranging from 0 to 2 points; after the booster immunization, the model group’s scores rose sharply, reaching as high as 13–14 points. In contrast, the control group maintained stable scores at 0 points.

 

 

Summary of Experience:

1. Controllability of the disease course: The CIA model has a modeling period of approximately 3–4 weeks, with a well-defined peak in disease onset, facilitating the design of an optimal time window for evaluating drug efficacy.

2. Stability: It exhibits a high incidence (>90%) in DBA/1 mice, with relatively synchronous disease progression.

3. Quality Control Criteria: Random sampling is conducted for each batch to assess joint swelling scores, ensuring phenotypic consistency prior to enrollment.

4. Past Completion: More than twenty CIA mouse models have been successfully established, with a success rate approaching 100%.