REG EXPRESSION OF CONSTITUTIVELY ACTIVE PKA

拟议的项目涉及开发一种靶向结构，该结构将产生蛋白激酶A（PKA）组成型活性形式的组织特异性表达。 检查这种不受调节的蛋白质在胚胎干细胞（ES细胞）中的表达相比，细胞表达正常或降低水平的PKA将使我们能够确定PKA在ES细胞增殖和分化成不同的细胞命运的作用。 这些靶向的ES细胞对小鼠生殖系的贡献将允许在实验控制条件下在特定组织中表达这种蛋白质。首先，我们计划研究这种组成型活性PKA酶在肥胖和体重调节中的作用，这些过程已知涉及PKA。 我们预测，在脂肪组织中表达PKA的这种组成性活性形式的小鼠将表现出瘦的表型，有助于我们对体重调节的理解，并提出可能的治疗人类肥胖的方法。

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.