Waschek J A
Department of Psychiatry, University of California, Los Angeles 90024-1759, USA.
Mol Neurobiol. 1995 Apr-Jun;10(2-3):205-17. doi: 10.1007/BF02740676.
A large number of neuroendocrine peptide genes have been tested for their ability to target expression to the hypothalamus and pituitary in transgenic mice. This has resulted in a number of powerful applications, for example, ablation or immortalization of specific cell types, and analysis of transcription regulatory sequences. The greatest amount of success in targeting cells of the neuroendocrine axis has been in the pituitary and has utilized regulatory sequences of genes that are normally expressed in pituitary. Greater difficulties have been encountered in directing expression to specific neurons in the hypothalamus. A primary goal of this review is to consider collectively the data obtained by a number of laboratories in order to draw conclusions about the general sequence requirements for achieving cell-specific expression. The data suggest that the mechanisms controlling cell-specific expression of neuropeptide genes in the hypothalamus are complex and involve multiple regulatory elements that may reside within the gene or many kilobases away from the promoter. These elements act positively and negatively in different cells to enhance or restrict expression, and may include sequences that shield a transgene from regulatory influences of other genes near the point of chromosomal insertion.
大量神经内分泌肽基因已在转基因小鼠中进行测试，以检验其将表达靶向至下丘脑和垂体的能力。这带来了许多强大的应用，例如，特定细胞类型的消融或永生化，以及转录调控序列的分析。在将神经内分泌轴的细胞作为靶向方面，取得最大成功的是垂体，并且利用了通常在垂体中表达的基因的调控序列。在将表达定向至下丘脑的特定神经元方面遇到了更大的困难。本综述的一个主要目标是综合考虑多个实验室获得的数据，以便就实现细胞特异性表达的一般序列要求得出结论。数据表明，控制下丘脑神经肽基因细胞特异性表达的机制很复杂，涉及多个调控元件，这些元件可能位于基因内部或距启动子数千碱基处。这些元件在不同细胞中发挥正向和负向作用，以增强或限制表达，并且可能包括使转基因免受染色体插入点附近其他基因调控影响的序列。
