Mouse models for human hyperuricaemia: a critical review

Last updated: 05-25-2019

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Mouse models for human hyperuricaemia: a critical review

Mouse models for human hyperuricaemia: a critical review
Nature Reviews Rheumatology (2019) | Download Citation
Subjects
Gout
Abstract
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.
Key points
Hyperuricaemia occurs mainly in higher primates, including in humans, primarily owing to inactivation of the uricase gene during primate evolution, which resulted in subsequent evolution of human-specific physiology to tolerate this inactivation.
Mouse models of hyperuricaemia have been widely used to provide valuable insights into urate biology but do not yet reliably and consistently simulate the urate-mediated hyperuricaemia that occurs in humans.
Such models are potentially valuable resources for dissecting the mechanisms underlying hyperuricaemia as well as the progression from hyperuricaemia to gout and associated comorbidities.
A key challenge is to develop uricase-disabled model mice that can survive with increased urate levels and remain healthy and fertile.
Community-wide efforts are needed to reach consensus about the definition of hyperuricaemia in mice, to develop protocols for generating suitable models of hyperuricaemia and to adhere to a standard protocol for urate measurements.
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Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
Jie Lu
 & Wen-Hua Wei
Shandong Provincial Key Laboratory of Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, the Affiliated Hospital of Qingdao University, Institute of Metabolic Diseases, Qingdao University, Qingdao, China
Jie Lu
Department of Medicine, University of Auckland, Auckland, New Zealand
Nicola Dalbeth
Chinese Academy of Sciences (CAS) Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences (SIBS), CAS, Shanghai, China
Huiyong Yin
Department of Biochemistry, University of Otago, Dunedin, New Zealand
Tony R. Merriman


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