A transgenic analysis of the physiologic roles of signalling domains in the growth hormone receptor

生长激素受体信号结构域生理作用的转基因分析

• 批准号: nhmrc : 252877
• 负责人: A/Pr Peter Noakes
• 金额: $ 17.5万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/transgenic-analysis-physiologic-hormone-receptor/77947
• 关键词: transgenic; analysis; physiologic; roles; signalling

The key hormone promoting growth postnatally is growth hormone (GH), and it acts through the growth hormone receptor to initiate a variety of signals which regulate gene expression. In addition to its role in growth, GH is an importnat metabolic regulator in starvation. It also appears to play a significant role in the ageing process, since mice lacking the GH receptor live 50% longer than normal mice. Although the signalling systems used by the GH receptor are reasonably well defined in vitro, we have no idea which signals are used to control postnatal growth, metabolism and ageing in the live animal. With NHMRC support, we have been creating mice with individual signalling domains of the GH receptor deleted. This proposal aims to use these mice to determine how the GH receptor brings about its actions of promoting postnatal growth, regulating metabolism and altering lifespan. In particular, through the use of gene arrays, we intend to define the key genes regulated in these processes. This would provide potential therapeutic targets for drug development to individually alter these key processes.

生长激素（growth hormone，GH）是促进出生后生长的关键激素，它通过生长激素受体启动多种信号调节基因表达。生长激素除了在生长中起作用外，在饥饿中也是一种重要的代谢调节因子。它似乎在衰老过程中也起着重要作用，因为缺乏GH受体的小鼠比正常小鼠寿命长50%。虽然GH受体所使用的信号系统在体外有相当好的定义，但我们不知道哪些信号用于控制活体动物的出生后生长，代谢和衰老。在NHMRC的支持下，我们已经创建了GH受体单个信号结构域缺失的小鼠。该提案旨在使用这些小鼠来确定GH受体如何发挥其促进出生后生长，调节代谢和改变寿命的作用。特别是，通过使用基因阵列，我们打算定义在这些过程中调节的关键基因。这将为药物开发提供潜在的治疗靶点，以单独改变这些关键过程。