SPROUTY, A WT1 TARGET FOR GROWTH AND DEVELOPMENT

描述：(改编自申请人的摘要) 在这个方案中，我们将描述Sprouty在肾脏中的表达 发育、小鼠发育和肾母细胞瘤。我们会 描述发芽的作用机制。因此我们将确定是否 Sprouty是一种生长抑制因子，可能参与WT1的部分作用。我们 将决定通过受体酪氨酸激酶传递信号的步骤 斯普鲁蒂表演。然后我们分离SPRY的配对蛋白，这将导致 对发芽的分子机制有更好的了解。为了确定 SPRY在正常和异常发育中的作用我们将在细胞中确定 SPRY基因工程表达的培养模型和转基因动物 干扰正常的肾脏形态发生。最后，提供一个关键角色 作为WT1的目标，芽对肾脏发育很重要，我们将创建 利用条件克隆技术将动物淘汰为发芽动物。穿过 在这些研究中，我们将描述一种与isgnal有关的令人兴奋的分子。 转导与发育。SPRY可能会成为未来战略的目标 治疗肾母细胞瘤、其他恶性肿瘤和多囊肾等肾脏疾病 肾脏疾病。

DESCRIPTION: (Adapted from the applicant's abstract) In this proposal we will characterize the expression of sprouty in renal development, murine development in general and in Wilm's tumors. We will characterize the mechanism of action of sprouty. Hence we will determine if sprouty is a growth inhibitor which may mediate some of the effects of WT1. We will determine at which steo in signaling through receptor tyrosine kinase sprouty acts. We then isolate partner proteins of spry which will lead to better idea of the molecular mechanism of sprouty. In order to determine the role of spry in normal and aberrant development we will determine in cell culture models and transgenic animals if engineered expression of spry interferes with normal renal morphogenesis. Finally to provide a critical role of sprouty as a target of WT1 important for renal development we will create knockout animals for sprouty one using conditiona cre-lox technology. Through these studies we will characterize an exciting molecule involved isgnal transduction and development. Spry may present a target for future strategies against Wilm's tumor, other malignancies and renal disorder such as polycystic kidney disease.