Mouse models for human hyperuricaemia: a critical review

Hyperuricaemia (increased serum urate concentration) occurs mainly in higher primates, including in humans, because of inactivation of the gene encoding uricase during primate evolution. Individuals with hyperuricaemia might develop gout - a painful inflammatory arthritis caused by monosodium urate crystal deposition in articular structures. Hyperuricaemia is also associated with common chronic diseases, including hypertension, chronic kidney disease, type 2 diabetes and cardiovascular disease. Many mouse models have been developed to investigate the causal mechanisms for hyperuricaemia. These models are highly diverse and can be divided into two broad categories: mice with genetic modifications (genetically induced models) and mice exposed to certain environmental factors (environmentally induced models; for example, pharmaceutical or dietary induction). This Review provides an overview of the mouse models of hyperuricaemia and the relevance of these models to human hyperuricaemia, with an emphasis on those models generated through genetic modifications. The challenges in developing and comparing mouse models of hyperuricaemia and future research directions are also outlined.