Developing Monosodium Urate Monohydrate Crystals-Induced Gout Model in Rodents and Rabbits

Gout is a chronic disease caused by the deposition of monosodium urate monohydrate (MSU) crystals within the body, particularly in one or more joints, which can lead to sudden severe attacks of pain, swelling, redness, and tenderness, known as gout flares. Historically termed the "disease of kings," gout is one of the oldest joint diseases and remains the most common form of inflammatory arthritis haunting humans in the 21^st century. It is associated with cardiovascular, metabolic, and renal comorbidities and can lead to reduced mobility and impaired physical function and contributing to work absenteeism. Given its increasing global incidence, novel therapies for gouty arthritis disease are urgently needed. Experimental gout models are indispensable tools for deciphering disease pathogenesis and evaluating the efficacy and side effect of newly developed therapeutics at preclinical stage. Herein, we described a series of highly reproducible acute gout flare and air pouch models in rodents and rabbits that can be used to address various scientific questions relevant to pathological changes and immune responses during and after a gout attack. Animal gout flare models, elicited by MSU crystals, mimic the main histopathological features of human gouty arthritis, including damage to cartilage and joint swelling. Meanwhile, air pouch models serve as a tool to evaluate robust inflammatory cytokine secretion and neutrophil infiltration. This article provides a detailed description of procedures and troubleshooting tips required to reproducibly induce gout flare and air pouch models in animals and critically evaluate the pathogenesis of the disease. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Preparation of monosodium urate crystalline Basic Protocol 2: Development of MSU-induced gout flare model in mice Support Protocol 1: Histological assessment of mouse ankle tissues Basic Protocol 3: Development of MSU-induced gout flare model in rats Basic Protocol 4: Development of MSU-induced gout flare model in rabbits Basic Protocol 5: Development and validation of reference articles in MSU-induced air pouch model in rats Basic Protocol 6: Development and validation of reference articles in MSU-induced air pouch model in mice Support Protocol 2: Flow cytometry of mouse neutrophils in air pouch lavage samples.