SPROUTY, A WT1 TARGET FOR GROWTH AND DEVELOPMENT

描述：（改编自申请人摘要） 在这个建议中，我们将描述肾脏中发芽的表达， 发育，一般的鼠发育和Wilm肿瘤。我们将 表征发芽的作用机制。因此，我们将确定，如果 发芽是一种生长抑制剂，可能介导WT 1的某些作用。我们 将决定通过受体酪氨酸激酶 愚蠢的行为然后我们分离出spry的伴侣蛋白， 对发芽的分子机制有了更好的认识。为了确定 我们将在细胞中确定spry在正常和异常发育中的作用， 培养模型和转基因动物， 干扰正常的肾脏形态发生。最后， 发芽作为WT 1的目标，对肾脏发育很重要，我们将创建 使用conditiona cre-lox技术敲除动物的sprougty 1。通过 这些研究我们将描述一个令人兴奋的分子参与isgnal 转导和发育。Spry可能会为未来的战略提出目标 针对肾母细胞瘤、其他恶性肿瘤和肾脏疾病，如多囊 肾病

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.