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Uncovering the earliest events leading to tophaceous gout

36 months
Approved budget:
Associate Professor Christopher Hall
Professor Nicola Dalbeth
Professor Graham Lieschke
Dr Tanja Linnerz
Health issue:
Proposal type:
Lay summary
Gout is the most common inflammatory arthritis in New Zealand, especially for Māori and Pacific people. Despite the antiquity of gout, for many patients treatment options remain limited. Hyperuricaemia leading to monosodium urate (MSU) crystal deposition in and around peripheral joints is the well-recognised cause of gout. A hallmark of long-standing disease is the formation of tophi that contribute to disability and poor health-related quality of life. How tophi form is very poorly understood due to a lack of suitable animal models. This proposal will leverage off a unique larval zebrafish model of gout that provides the only whole animal system where the host response to MSU crystals can be directly observed. Exploiting this model, we will uncover the cellular and molecular mechanisms underpinning tophus formation. In addition to solving one of the remaining mysteries of gout pathogenesis, this new knowledge may reveal innovative strategies to treat tophaceous gout.