The HPH-1 mouse:: A model for dominantly inherited GTP-cyclohydrolase deficiency
The HPH-1 mouse:: A model for dominantly inherited GTP-cyclohydrolase deficiency
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DOI：
10.1002/ana.10695
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发表时间：
2003-01-01
影响因子：
11.2
通讯作者：
Engle, T
中科院分区：
文献类型：
--
作者：
Hyland, K;Gunasekara, RS;Engle, T
显性遗传性鸟苷三磷酸(GTP)-环水解酶缺乏症，也被称为Segawa病或多巴反应性肌张力障碍，具有从无症状到非常严重的广泛的表型表达。与男性相比，女性的外显率更高，症状强度的昼夜变化也是多变的。该病的生化特征显示，脑脊液中四氢生物蝶呤(BH4)、新喋呤和高香草酸水平较低，纹状体中酪氨酸羟基酶蛋白水平较低。为了研究其病理生理机制，我们已经开始研究GTP环水解酶缺陷HPH-1小鼠的生物胺和BH4代谢。数据显示，大脑中BH4、儿茶酚胺、5-羟色胺及其代谢物的水平较低，纹状体中的酪氨酸羟基酶蛋白水平较低。因此，HPH-1小鼠为研究人类疾病提供了一个很好的模型系统。
Dominantly inherited guanosine triphosphate (GTP)-cyclohydrolase deficiency, otherwise known as Segawa's disease or dopa-responsive dystonia, has a wide spectrum of phenotypic expression ranging from asymptomatic to very severe. Penetrance is more frequent in women as compared with men, and there is a variable occurrence of diurnal variation in symptom intensity. Biochemical characterization of the disease has demonstrated lower cerebrospinal fluid levels of tetrahydrobiopterin (BH4), neopterin, and homovanillic acid and low levels of tyrosine hydroxylase protein in the striatum. To investigate the pathophysiology, we have begun to characterize biogenic amine and BH4 metabolism in the GTP cyclohydrolase deficient hph-1 mouse. The data show low brain levels of BH4, catecholamines, serotonin, and their metabolites together with low levels of tyrosine hydroxylase protein within the striatum. The hph-1 mouse therefore provides a good model system in which to study the human disease.