Stout J T, Chen H Y, Brennand J, Caskey C T, Brinster R L
Nature. 1985;317(6034):250-2. doi: 10.1038/317250a0.
Severe deficiency of hypoxanthine phosphoribosyltransferase (HPRT) in man results in the Lesch-Nyhan syndrome, an X-linked neurological disorder characterized by mental retardation, choreoathetosis and a compulsive tendency towards self-mutilation. Although the HPRT gene is normally constitutively expressed in all tissues at low levels, expression is elevated approximately fourfold in several regions of the central nervous system, particularly in the basal ganglia. The relationships between HPRT deficiency, tissue-specific alterations of nucleotide metabolism and the neuropathology of the Lesch-Nyhan syndrome remain unclear. Here we have microinjected recombinant molecules containing human HPRT (hHPRT) complementary DNA, the mouse metallothionein-I (MT-I) promoter and the 3'-untranslated portion of the human growth hormone (hGH) gene into mouse embryos to produce transgenic animals that express hHPRT on induction by cadmium. The hHPRT cDNA in these experiments contained 88 base pairs (bp) of 5'-untranslated and 190 bp of 3'-untranslated sequences, and the full-length coding sequence. We studied the in vivo expression of this MT-hHPRT fusion gene and observed preferential hHPRT expression in tissues of the central nervous system (CNS). This study suggests that sequences within the hHPRT transcript (cDNA) influence CNS expression via increased synthesis or stability of messenger RNA.
人类次黄嘌呤磷酸核糖基转移酶（HPRT）严重缺乏会导致莱施-奈恩综合征，这是一种X连锁神经疾病，其特征为智力迟钝、舞蹈手足徐动症以及自残的强迫倾向。尽管HPRT基因通常在所有组织中以低水平组成性表达，但在中枢神经系统的几个区域，尤其是基底神经节中，其表达会升高约四倍。HPRT缺乏、核苷酸代谢的组织特异性改变与莱施-奈恩综合征神经病理学之间的关系仍不清楚。在这里，我们将包含人类HPRT（hHPRT）互补DNA、小鼠金属硫蛋白-I（MT-I）启动子和人类生长激素（hGH）基因3'非翻译部分的重组分子显微注射到小鼠胚胎中，以产生在镉诱导下表达hHPRT的转基因动物。这些实验中的hHPRT cDNA包含88个碱基对（bp）的5'非翻译序列和190 bp的3'非翻译序列以及全长编码序列。我们研究了这种MT-hHPRT融合基因的体内表达，并观察到hHPRT在中枢神经系统（CNS）组织中的优先表达。这项研究表明，hHPRT转录本（cDNA）中的序列通过增加信使RNA的合成或稳定性来影响中枢神经系统的表达。
