描述的老鼠和人类三磷酸鸟苷cyclohydrolase我基因。突变患者三磷酸鸟苷cyclohydrolase我缺乏。
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Ichinose H, Ohye T,松田Y, Hori T,布劳N, Burlina,唤醒B, Matalon R, Fujita K, Nagatsu T
描述的老鼠和人类三磷酸鸟苷cyclohydrolase我基因。突变患者三磷酸鸟苷cyclohydrolase我缺乏。
J生物化学杂志。1995年4月28日,270 (17):10062 - 71。
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7730309 (在PubMed]
- 文摘
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三磷酸鸟苷cyclohydrolase我是第一个和病原反应酶的生物合成四氢生物蝶呤在哺乳动物。以前,我们报告三种人类三磷酸鸟苷cyclohydrolase我cDNA在人类肝cDNA文库(Togari,。Ichinose, H。松本,S。藤田,K。学生物化学,Nagatsu t (1992)。Biophys。Commun >, 187年,359 - 365)。此外,最近,我们发现三磷酸鸟苷cyclohydrolase我基因的遗传性进行性肌张力障碍病因昼夜波动,也称为DOPA-responsive肌张力障碍(Ichinose H。Ohye, T。高桥E。塞其N。Hori T。,Segawa M。,野村证券(Nomura) Y。Endo, K。田中,H。信,S。, Fujita, K., and Nagatsu, T. (1994) Nature Genetics 8, 236-242). To clarify the mechanisms that regulate transcription of the GTP cyclohydrolase I gene and to generate multiple species of mRNA, we isolated genomic DNA clones for the human and mouse GTP cyclohydrolase I genes. Structural analysis of the isolated clones revealed that the GTP cyclohydrolase I gene is encoded by a single copy gene and is composed of six exons spanning approximately 30 kilobases. We sequenced all exon/intron boundaries of the human and mouse genes. Structural analysis also demonstrated that the heterogeneity of GTP cyclohydrolase I mRNA is caused by an alternative usage of the splicing acceptor site at the sixth exon. The transcription start site of the mouse GTP cyclohydrolase I gene and the 5'-flanking sequences of the mouse and human genes were determined. We performed regional mapping of the mouse gene by fluorescence in situ hybridization, and the mouse GTP cyclohydrolase I gene was assigned to region C2-3 of mouse chromosome 14. We identified missense mutations in patients with GTP cyclohydrolase I deficiency and expressed mutated enzymes in Escherichia coli to confirm alterations in the enzyme activity.