New animal model of chronic gout reproduces pathological features of the disease in humans

RMD Open. 2023 Nov;9(4):e003499. doi: 10.1136/rmdopen-2023-003499.

Abstract

Objectives: Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans.

Methods: A novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed.

Results: After 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori's methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice.

Conclusions: Our model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.

Keywords: Antirheumatic Agents; Arthritis, Experimental; Gout.

MeSH terms

  • Animals
  • Arthritis, Gouty* / chemically induced
  • Arthritis, Gouty* / drug therapy
  • Arthritis, Gouty* / pathology
  • Disease Models, Animal
  • Gout Suppressants / adverse effects
  • Gout* / drug therapy
  • Humans
  • Mice
  • Uric Acid

Substances

  • Uric Acid
  • Gout Suppressants