Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice.
Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice.
复制标题
神经元一氧化氮在 HPRT 缺陷小鼠多巴胺缺乏中的作用。
DOI：
10.1007/s11011-007-9044-7
复制
发表时间：
2007
影响因子：
3.6
通讯作者：
Jinnah,HyderA
中科院分区：
文献类型：
--
作者：
Smith,DougW;Jinnah,HyderA
莱施-尼汉病是一种因嘌呤补救活性缺乏而引起的衰弱性疾病。患者和次黄嘌呤磷酸核糖转移酶（HPRT）突变小鼠均表现出基底神经节多巴胺缺乏。我们以前报道过HPRT缺陷小鼠脑中氧化剂敏感酶的活性降低。在本研究中，我们已经调查了自由基的来源之一，神经元型一氧化氮合酶（NOS 1），是否有助于与HPRT缺乏相关的多巴胺缺陷。繁殖HPRT敲除小鼠和野生型小鼠，使其缺乏或具有完整的NOS 1等位基因。双突变小鼠的纹状体多巴胺和多巴胺代谢物水平与HPRT单突变小鼠没有区别。这些结果表明，NOS 1产生的一氧化氮不会导致HPRT缺乏症中的多巴胺缺乏。
Lesch-Nyhan disease is a debilitating disorder caused by a lack of purine salvage activity. Basal ganglia dopamine deficits manifest in both patients and hypoxanthine phosphoribosyltransferase (HPRT) mutant mice. We previously reported decreased activity in an oxidant sensitive enzyme in the brain of HPRT-deficient mice. In the present study, we have investigated whether one source of free radicals, neuronal nitric oxide synthase (NOS1), contributes to the dopamine deficit associated with HPRT deficiency. HPRT knockout and wild-type mice were bred, either to lack, or to have the full complement of NOS1 alleles. Double mutant mice had striatal dopamine and dopamine metabolite levels indistinguishable from the HPRT single mutant counterparts. These results indicate that NOS1 produced nitric oxide does not contribute to the dopamine deficit seen in HPRT deficiency.