Targeted Disruption of L-Proline Transporter Gene by Homolgous Recombination

通过同源重组靶向破坏 L-脯氨酸转运蛋白基因

• 批准号: 9310965
• 负责人: Robert Fremeau, Jr.
• 金额: $ 4.86万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1994-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9310965&HistoricalAwards=false
• 关键词: Targeted; Disruption; Proline; Transporter; Gene

Many of the most exciting technical advances in neurobiology have come from the field of genetic engineering. It is now possible to selectively "knock out" single genes and examine their effect on behavior. Knock-out mice, as they are called, have been used to probe the circuits underlying learning and memory, temperature adaptation, and many other behaviors. They provide highly selective probes for elucidating the long mysterious connection between genes and behavior. Dr. Fremeau has recently cloned the gene for a high-affinity membrane transporter for proline. The fact that these uptake systems for proline are found in selective populations of glutaminergic nerve terminals suggests that proline is a novel neurotransmitter which modifies glutaminergic transmission in some way. Since glutamate is a major transmitter in cerebral cortex and involved in mechanisms of neuroplasticity, it is obviously of great interest to determine proline's role in glutaminergic function. This NSF small grant for exploratory research (SGER) will give Dr. Fremeau the chance to use genetic engineering techniques to solve this problem. He will attempt the high-risk/high gain task of producing a knock out mouse that lacks this membrane component. If he succeeds it will be possible to determine the role that proline neurotransmission plays in the development of behavior. This is the kind of research for which the SGER was designed for there are few other funding mechanisms for supporting research that does not have a fairly assured payoff.***//

神经生物学中许多最令人兴奋的技术进步 来自基因工程领域。 现在可以 选择性地“敲除”单个基因， 行为 基因敲除小鼠，正如他们所说的，已经被用来 探索学习和记忆、温度 适应，以及其他许多行为。 他们提供了高度 选择性的探测器来阐明 基因和行为之间的联系 Fremeau博士最近克隆了 脯氨酸高亲和力膜转运蛋白基因。 的 事实上，这些脯氨酸的摄取系统被发现在选择性 多巴胺能神经末梢的数量表明， 是一种新的神经递质， 以某种方式传播。 由于谷氨酸是一种主要的 参与神经可塑性机制， 很明显，确定脯氨酸在 多巴胺能功能。 NSF小额资助用于探索 研究（SGER）将使Fremeau博士有机会使用遗传 工程技术来解决这个问题。 他将尝试 高风险/高收益的任务，生产敲除小鼠，缺乏 这个膜的成分。 如果他成功了， 确定脯氨酸神经传递的作用， 行为的发展。 这种研究 SGER的设计是因为很少有其他的融资机制 支持那些没有一个公平保证的研究， payoff.*//