REG EXPRESSION OF CONSTITUTIVELY ACTIVE PKA

本构型活性 PKA 的 REG 表达

• 批准号: 6362971
• 负责人: COLLEEN M NISWENDER
• 金额: $ 4.19万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6362971
• 关键词: adipose tissue; body temperature; cell differentiation; enzyme activity; gene expression; gene mutation; genetically modified animals; laboratory mouse; metabolism; protein kinase A; site directed mutagenesis; transfection

The proposed project involves developing a targeting construct that will generate tissue-specific expression of a constitutively active form of protein kinase A (PKA). Examination of the expression of this unregulated protein in embryonic stem cells (ES cells) compared to cells expressing either normal or decreased levels of PKA will allow us to determine the role of PKA in ES cell proliferation and differentiation into distinct cell fates. Contribution of these targeted ES cells to the germline of mice will permit expression of this protein in specific tissues under experimentally controlled conditions. Preliminarily, we plan to study the effect of this constitutively active PKA enzyme in the regulation of adiposity and weight regulation, processes that are known to involve PKA. We predict that mice expressing this constitutively active form of PKA in adipose tissue will exhibit a lean phenotype, contributing to our understanding of body weight regulation and suggesting possible treatments for obesity in humans.

所提出的项目涉及开发靶向构建体，该构建体将产生蛋白激酶A（PKA）组成型活性形式的组织特异性表达。 与表达正常水平或降低PKA水平的细胞相比，该不调节蛋白在胚胎干细胞（ES细胞）中的表达的检查将使我们能够确定PKA在ES细胞增殖中的作用，并分化为不同的细胞命运。 这些靶向ES细胞对小鼠种系的贡献将允许在实验控制的条件下在特定组织中表达该蛋白质。首先，我们计划研究这种组成型活性PKA酶对肥胖和体重调节调节的影响，即已知涉及PKA的过程。 我们预测，在脂肪组织中表达这种组成型活性形式的小鼠将表现出瘦表型，这有助于我们对体重调节的理解，并提出可能治疗人类肥胖症的可能治疗方法。