5'-flanking sequences of the human HPRT gene direct neuronal expression in the brain of transgenic mice.
5'-flanking sequences of the human HPRT gene direct neuronal expression in the brain of transgenic mice.
复制标题
人类 HPRT 基因的 5 侧翼序列指导转基因小鼠大脑中的神经元表达。
DOI：
10.1002/jnr.490380304
复制
发表时间：
1994
影响因子：
4.2
通讯作者：
Patel,PI
中科院分区：
文献类型：
--
作者：
Rincon-Limas,DE;Geske,RS;Xue,JJ;Hsu,CY;Overbeek,PA;Patel,PI
人类次黄嘌呤磷酸核糖转移酶（HPRT）的完全缺乏导致神经系统疾病Lesch-Nyhan综合征。HPRT基因在所有组织中以基础水平表达，但在脑中以较高水平表达，其相关性和机制尚不清楚。为了确定顺式作用DNA元件是否在表达的组织差异模式中发挥作用，我们产生了携带不同序列的人HPRT（hHPRT）启动子融合到bacteriallacZ基因的转基因小鼠。我们发现，hHPRT启动子的1.6 kb片段包含指导β-半乳糖苷酶表达的基本信息，优先在基底神经节，大脑皮层，海马和前脑的其他几个区域。1.6 kb片段内至少有两个元件似乎是神经元表达所需的。182 bp元件（hHPRT-NE）代表这些序列之一，不仅参与赋予神经元特异性，还参与抑制非神经元组织中的转基因表达。这些研究提供了对脑中HPRT表达增加的机制的分子见解。© 1994 Wiley利斯公司
Total deficiency of hypoxanthine phosphoribosyl‐transferase (HPRT) in humans causes the neurological disorder Lesch‐Nyhan syndrome. The HPRT gene is expressed at basal levels in all tissues but at higher levels in the brain, the relevance and mechanism of which is unknown. To determine ifcis‐acting DNA elements play a role in the tissue‐differential pattern of expression, we generated transgenic mice carrying different sequences of the human HPRT (hHPRT) promoter fused to the bacteriallacZgene. We show that a 1.6 kb fragment of the hHPRT promoter contains essential information to direct β‐galactosidase expression preferentially to the basal ganglia, cerebral cortex, hippocampus, and several other areas of the forebrain. At least two elements within the 1.6 kb fragment appear to be required for neuronal expression. A 182 bp element (hHPRT‐NE) represents one of those sequences and is involved not only in confering neuronal specificity but also in repressing transgene expression in non‐neuronal tissues. These studies provide molecular insight into the mechanism of increased HPRT expression in the brain. © 1994 Wiley‐Liss, Inc.