Immortalization of Hypothalamic Gonadotropin-Releasing Hormone Neurons Using Targeted Oncogene Expression in Transgenic Mice

Weiner Richard L., Moenter Suzanne M.
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Abstract

Three clonal gonadotropin-releasing hormone (GnRH) neuronal cell lines were derived from a genetically induced tumor in transgenic mice. A transgene was constructed to target expression of simian virus 40 T antigen to GnRH neurons using the promoter/enhancer domains of the cell-specifically expressed GnRH gene. The resulting GT1 cells were characterized by morphology, the expression of neuron-specific genes, expression and processing of GnRH, pulsatile basal secretion of GnRH, release of GnRH in response to depolarization, and regulation of GnRH release by a variety of neurotransmitters and neuromodulators. By all of these criteria, GT1 cells are highly differentiated neuronal cell lines that provide valuable models for studying the cell biology of neuroendocrine cells.

靶向癌基因表达对转基因小鼠下丘脑促性腺激素释放激素神经元的永生作用
从转基因小鼠的基因诱导肿瘤中获得了三种克隆性促性腺激素释放激素(GnRH)神经元细胞系。构建转基因以利用特异性表达GnRH基因的细胞的启动子/增强子结构域靶向GnRH神经元表达猴病毒40T抗原。所产生的GT1细胞的特征是形态、神经元特异性基因的表达、GnRH的表达和处理、GnRH脉动的基础分泌、GnRH对去极化的释放以及多种神经递质和神经调节剂对GnRH释放的调节。根据所有这些标准,GT1细胞是高度分化的神经元细胞系,为研究神经内分泌细胞的细胞生物学提供了有价值的模型。
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