Abstract Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in HGprt enzyme activity can lead to the neurological syndrome, especially the self-injury of LND. Several studies have proposed different hypotheses regarding the etiology of this disease, and several treatments have been tried in patients. However, up to now, there is no satisfactory explanation of the disease and for many LND patients, efficacious treatment for persistent self-injurious behavior remains unreachable. A role for epistasis between mutated hypoxanthine phosphoribosyltransferase 1 (HPRT1) and amyloid precursor protein (APP) genes has been recently suggested. This finding may provide new directions not only for investigating the role of APP in neuropathology associated with HGprt-deficiency in LND but also for the research in neurodevelopmental and neurodegenerative disorders in which the APP gene is involved in the pathogenesis of diseases and may pave the way for new strategies applicable to rational antisense drugs design. It is therefore necessary to study the HGprt enzyme and APP using expression vectors for exploring their impacts on LND as well as other human diseases, especially the ones related to APP such as Alzheimer’s disease in which the physiologic function and the structure of the entire APP remain largely unclear until now. For such a purpose, we report here the construction of expression vectors as the first step (Part I) of our investigation.

中文翻译：

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Lesch-Nyhan病：一、次黄嘌呤鸟嘌呤磷酸核糖转移酶（HGprt）和淀粉样前体蛋白（APP）表达载体的构建

摘要 Lesch-Nyhan 病 (LND) 是一种罕见的 X 连锁遗传性嘌呤代谢神经遗传性疾病，其中次黄嘌呤鸟嘌呤磷酸核糖转移酶 (HGprt) 存在缺陷。尽管在 50 多年前就已被表征，但目前尚不清楚 HGprt 酶活性的缺陷如何导致神经系统综合征，尤其是 LND 的自伤。几项研究提出了关于这种疾病病因的不同假设，并且已经在患者中尝试了几种治疗方法。然而，到目前为止，对该病还没有令人满意的解释，对于许多 LND 患者来说，对持续性自伤行为的有效治疗仍然遥不可及。 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 最近有人提出突变的次黄嘌呤磷酸核糖基转移酶 1 (HPRT1) 和淀粉样前体蛋白 (APP) 基因之间的上位作用。这一发现不仅可以为研究APP在与LND中HGprt缺陷相关的神经病理学中的作用提供新的方向，而且可以为APP基因参与疾病发病机制的神经发育和神经退行性疾病的研究提供新的方向，并可能铺平道路适用于合理反义药物设计的新策略。因此，有必要使用表达载体研究HGprt酶和APP，以探索它们对LND以及其他人类疾病的影响，尤其是与APP相关的疾病，如阿尔茨海默病，其中整个APP的生理功能和结构仍然存在直到现在基本不清楚。