Directed expression of an oncogene to the olfactory neuronal lineage in transgenic mice

Directed expression of an oncogene to the olfactory neuronal lineage in transgenic mice
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致癌基因在转基因小鼠嗅觉神经元谱系中的定向表达

DOI:
10.1523/jneurosci.13-01-00300.1993
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发表时间:
1993
期刊:
影响因子:
4.4
通讯作者:
R. Reed
R. Reed
中科院分区:
医学2区
文献类型:
--
作者:
B. Largent;R. Sosnowski;R. Reed

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哺乳动物的嗅觉系统为理解神经系统发育的细胞和分子机制提供了有用的模型。在成年动物中,嗅觉神经上皮经历了持续的更替,导致神经组织含有处于神经发生不同阶段的细胞。我们已经建立了一个转基因小鼠系来检验在嗅神经细胞谱系中定向表达癌基因的效果。利用嗅觉标记蛋白基因的调控元件,构建了一个混合癌基因,用于指导猴病毒40T抗原的嗅神经元特异性表达。由此产生的转基因小鼠株系只在嗅神经元中表达T抗原。10月龄转基因小鼠嗅神经上皮神经元成分明显发育不良。转基因小鼠患上低频率的嗅神经源性神经母细胞瘤。不同的克隆系来自肿瘤的原代培养。生长相关神经元标记物GAP-43在部分细胞系中表达。其中一个细胞系2.2似乎对假定的目标组织--嗅球--的神经营养效应有反应。
The mammalian olfactory system provides a useful model to understand the cellular and molecular mechanisms governing the development of the nervous system. The olfactory neuroepithelium undergoes continual turnover in the adult animal, resulting in a neural tissue containing cells at various stages of neurogenesis. We have generated a transgenic mouse line to examine the effects of directed expression of an oncogene within the olfactory neuronal lineage. A hybrid oncogene was constructed utilizing the regulatory elements for the olfactory marker protein gene to direct the olfactory neuronal-specific expression of simian virus 40 T-antigen, a potent oncogene. The resulting transgenic mouse line expressed T-antigen only in olfactory neurons. Ten-month-old transgenic mice displayed significant hypoplasia of the neuronal elements in the olfactory neuroepithelium. The transgenic mice developed neuroblastomas of olfactory neuronal origin at a low frequency. Distinct clonal lines were derived from the primary culture of the tumor. GAP-43, a growth-associated neuronal marker, was expressed by some of the cell lines. One of the cell lines, 2.2, appeared to be responsive to neurotrophic effects from the presumptive target tissue, the olfactory bulb.
DOI: 10.1016/0165-3806(90)90132-i
发表时间: 1990-04
期刊: Brain research. Developmental brain research
影响因子: --
作者:
S. Pixley;R. Pun
通讯作者: S. Pixley;R. Pun