PLATELET DERIVED GROWTH FACTOR-ALPHA RECEPTOR

血小板衍生生长因子（PDGF）已被认为是一种 在正常发育过程中驱动增殖的生长因子， 在各种病理条件下，包括血管反应， 损伤、高血压和动脉粥样硬化。 支持这些假设 在很大程度上是间接的，通常包括观察到的 血小板源性生长因子及其表达与细胞增殖的相关性 受体。 我们建议开发“嵌合”小鼠作为直接 评估PDGF/PDGF受体系统的组分在 vivo. 嵌合小鼠是通过将来自 两个不同的胚胎 我们的第一个目标是创造嵌合体， 这两个组件都是正常的，但其中一个被标记为这样一种方式， 两个分量的导数可以明确区分。 这些嵌合体将被用来获得关于进入方式的基本信息 正常细胞在发育过程中增殖和迁移， 血管壁和病理变化。 然后我们将准备 标记的正常细胞和突变细胞之间的嵌合体，并使用这些 调查消除化学品成分的后果 PDGF/PDGF受体系统。 我们将开始调查的作用， 使用Patch突变体的PDGF受体α-亚基（PDGFR α）。 我们 已经证明Patch突变会删除PDGFR α基因。 我们将 使用我们从Patch突变胚胎中获得的细胞系， 嵌合小鼠胚胎，其中没有PDGFRalpha基因的细胞可以 存活并在组织学上（使用标记物）与细胞区分 携带PDGFR α基因。 通过比较相邻的 受体阳性和受体阴性细胞，我们将能够 直接评估PDGFR α在发展中的作用， 血管系统，以及血管细胞对 病理性扰动，包括损伤、高血压和 动脉粥样硬化 在时间允许的情况下， PDGFR α分析将用于评价其他 PDGF/PDGF受体系统的组成部分，从PDGF 受体β亚基（PDGFRbeta）。 根据他的表情 在这两种PDGF受体蛋白中，我们预计PDGFR β 突变体在发育过程中的作用较小， 在成人病理条件下介导细胞反应。

Platelet-derived growth factor (PDGF) has been proposed to be one of the growth factors which drive proliferation during normal development and in various pathological conditions, including vascular response to injury, hypertension, and atherosclerosis. Support for these hypotheses has been largely circumstantial, usually consisting of an observed correlation between proliferation and expression of PDGF and PDGF receptors. We propose to develop "chimeric" mice as tools for directly evaluating the role of components of the PDGF/PDGF receptor system in vivo. Chimeric mice are created by combining early embryonic cells from two different embryos. Our first goal will be to create chimeras in which both components are normal but one is marked in such a way that derivatives of the two components can be distinguished unambiguously. These chimeras will be used to obtain basic information about the way in which normal cells proliferate and migrate during the development of the vessel wall and during pathological changes. We will then prepare chimeras between marked normal and mutant cells and use these to investigate the consequences of elimination of components of the PDGF/PDGF receptor system. We will begin by investigating the role of the PDGF receptor alpha-subunit (PDGFRalpha) using the Patch mutant. We have shown that the Patch mutation deletes the PDGFRalpha gene. We will use cell lines that we have derived from Patch mutant embryos to create chimeric mouse embryos in which cells without the PDGFRalpha gene can survive and be distinguished histologically (using the marker) from cells with the PDGFRalpha gene. By comparing the behavior of adjacent receptor-positive and receptor-negative cells, we will be able to directly evaluate the role that PDGFRalpha plays in the development of the vascular system, and in the response of vascular cells to pathological perturbations, including injury, hypertension, and atherogenesis. As time permits, the techniques and reagents developed for analysis of PDGFRalpha will be used to evaluate the role of other components of the PDGF/PDGF receptor system, beginning with the PDGF receptor beta-subunit (PDGFRbeta). Based on the pattern of expression of the two PDGF receptor proteins, we anticipate that the PDGFRbeta mutants will have a lesser role during development and a greater role in mediating cell responses in adult pathological conditions.