REG EXPRESSION OF CONSTITUTIVELY ACTIVE PKA

拟议的项目涉及开发一种靶向构建体，该构建体将产生一种具有结构性活性的蛋白激酶A(PKA)的组织特异性表达。检测这种非调控蛋白在胚胎干细胞(ES细胞)中的表达与表达正常或降低的PKA的细胞相比，将使我们能够确定PKA在ES细胞增殖和分化为不同细胞命运中的作用。这些靶向ES细胞对小鼠生殖系的贡献将允许在实验控制的条件下在特定组织中表达这种蛋白。初步，我们计划研究这种具有结构性活性的PKA酶在调节肥胖和体重调节中的作用，这是已知涉及PKA的过程。我们预测，在脂肪组织中表达这种结构性活性形式的PKA的小鼠将表现出瘦削的表型，这有助于我们理解体重调节，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.