REG EXPRESSION OF CONSTITUTIVELY ACTIVE PKA

拟议的项目涉及开发一种靶向构建物，该构建物将产生一种组成活性形式的蛋白激酶a （PKA）的组织特异性表达。将胚胎干细胞（ES细胞）中这种不调节蛋白的表达与表达正常或降低PKA水平的细胞进行比较，将使我们能够确定PKA在ES细胞增殖和分化成不同细胞命运中的作用。将这些目标胚胎干细胞移植到小鼠的种系中，可以在实验控制的条件下在特定组织中表达这种蛋白质。初步，我们计划研究这种组成活性PKA酶在肥胖和体重调节中的作用，这些过程已知与PKA有关。我们预测，在脂肪组织中表达这种组成活性形式的PKA的小鼠将表现出瘦表型，有助于我们对体重调节的理解，并为人类肥胖的可能治疗提供建议。

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.