Lesch-Nyhan disease: from mechanism to model and back again
Lesch-Nyhan disease: from mechanism to model and back again
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DOI：
10.1242/dmm.002543
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发表时间：
2009-03-01
影响因子：
4.3
通讯作者：
Jinnah, H. A.
中科院分区：
文献类型：
--
作者：
Jinnah, H. A.
莱-尼二氏病（LND）是一种罕见的遗传性疾病，由编码次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）的基因突变引起。LND的特征是尿酸产生过多，导致痛风性关节炎和肾结石。受影响的患者也有特征性的神经和行为异常。已经开发了多种细胞模型来研究LND的分子和代谢方面，并且已经开发了几种动物模型来阐明神经行为综合征的基础。这些模型具有不同的优点和缺点，使它们适合研究疾病的不同方面。LND中广泛的建模工作质疑了“理想”疾病模型是复制其所有特征的模型的概念，因为疾病的不同要素的发病机制涉及不同的机制。相反，建模工作提出了一种更富有成效的方法，包括开发特定的模型，每个模型都是针对特定的实验问题而定制的。
Lesch-Nyhan disease (LND) is a rare inherited disorder caused by mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT). LND is characterized by overproduction of uric acid, leading to gouty arthritis and nephrolithiasis. Affected patients also have characteristic neurological and behavioral anomalies. Multiple cell models have been developed to study the molecular and metabolic aspects of LND, and several animal models have been developed to elucidate the basis for the neurobehavioral syndrome. The models have different strengths and weaknesses rendering them suitable for studying different aspects of the disease. The extensive modeling efforts in LND have questioned the concept that an 'ideal' disease model is one that replicates all of its features because the pathogenesis of different elements of the disease involves different mechanisms. Instead, the modeling efforts have suggested a more fruitful approach that involves developing specific models, each tailored for addressing specific experimental questions.