高尿酸血症
尿酸氧化酶
尿酸
痛风
尿囊素
内分泌学
内科学
肾病
生物化学
生物
化学
医学
糖尿病
作者
Xiangwei Wu,Maki Wakamiya,Sukeshi Vaishnav,Robert S. Geske,Charles A. Montgomery,Paula G. Jones,Allan Bradley,C. Thomas Caskey
标识
DOI:10.1073/pnas.91.2.742
摘要
Urate oxidase, or uricase (EC 1.7.3.3), is a purine metabolic enzyme that catalyzes the conversion of uric acid to allantoin in most mammals except humans and certain other primates. The loss of urate oxidase in the human during primate evolution predisposes man to hyperuricemia, a metabolic disturbance that can lead to gouty arthritis and renal stones. To create a mouse model for hyperuricemia and gout, and to address the question of whether urate oxidase is essential in lower mammalian species, we have disrupted the urate oxidase gene in the mouse by homologous recombination in embryonic stem cells. Unlike the human situation, urate oxidase deficiency in mice causes pronounced hyperuricemia and urate nephropathy. More than half of the mutant mice died before 4 weeks of age, indicating that urate oxidase is essential in mice. These mutant mice may also serve as animal models for hyperuricemia and its related nephropathy in humans.
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