Vasopressin gene expression: experimental models and strategies.
Vasopressin gene expression: experimental models and strategies.
复制标题
加压素基因表达：实验模型和策略。
DOI：
10.1006/exnr.2001.7769
复制
发表时间：
2001
影响因子：
5.3
通讯作者：
House,SB
中科院分区：
文献类型：
--
作者：
Gainer,H;Fields,RL;House,SB
分离加压素（VP）和催产素（OT）基因的基因间区（IGR）已被证明对这些肽基因在下丘脑神经元中的细胞特异性表达至关重要。到目前为止，最相关的信息IGR中的推定顺式元件，可能会决定细胞特异性基因表达来自转基因模型的研究。作为提高转基因动物中IGR序列缺失研究效率的第一步，使用比较基因组学方法比较人与小鼠中的IGR序列来鉴定可能是候选调控元件的保守序列。对人VP和OT基因IGR的核苷酸序列进行了测定，并与小鼠IGR进行了比较，发现了3个不同簇的26个保守序列，这些保守序列和基序可能对VP和OT基因的细胞特异性表达具有重要意义。然而，在取得进一步的重大进展之前，需要一种用于在体外分析相关细胞类型中的缺失构建体的“高通量”方法。在这里提出，结合使用粒子介导的基因转移方法的器官型培养模型，可以提供一个有效的，一般的策略，在中枢神经系统中的细胞特异性表达的研究。
The intergenic region (IGR) separating the genes for vasopressin (VP) and oxytocin (OT) has been shown to be critical for the cell-specific expression of these peptide genes in hypothalamic neurons. To date, the most relevant information about the putative cis-elements in the IGR that might determine cell-specific gene expression has come from studies in transgenic models. As a first step toward increasing the efficiency of the IGR sequence deletion studies in transgenic animals, a comparative genomics approach comparing the IGR sequence in humans versus mice was used to identify conserved sequences that might be candidate regulatory elements. The nucleotide sequence of the IGR between the human VP and OT genes was determined and compared to the mouse IGR, and 26 conserved sequences in three distinct clusters were found. These conserved sequences and motifs may be important for the cell-specific expression of the VP and OT genes. However, before further significant progress can be made, a “high-throughput” method for the analysis of deletion constructs in relevant cell types in vitro is needed. It is proposed here that organotypic culture models combined with the use of particle-mediated gene transfer methods may provide an effective, general strategy for the study of cell-specific expression in the central nervous system.