Mouse Model For Amniotic Fluid Volume Regulation

描述（由申请人提供）：全面了解 控制羊水量具有重要的临床意义。我们有 以前确定了一个血管通路内的胎膜为 液体从羊膜腔转移到胎儿血液中。这 该通路由微血管的网络构成，所述微血管的网络位于血管的表面上。 胎盘内，绵羊的羊膜和绒毛膜内也有。我们假设 血管内皮生长因子（VEGF）是 这种膜内途径的吸收能力，因此是一个重要的 羊水量的调节器。在本申请中，我们提出 建立羊水过多和羊水过少的小鼠模型。该车型将 使用靶向抑制或诱导VEGF基因表达来产生， 胎膜和胎盘小鼠模型的优点在于， 允许研究VEGF在膜内吸收中的作用， 操纵提出了三个具体目标。具体目标1： 通过使用VEGF抑制VEGF基因表达产生羊水过多 VEGF反义序列与羊水过少的关系 膜和胎盘。胎儿肺发育异常， 将研究羊水量的变化。第2章调查 羊膜、绒毛膜和胎盘中微血管的增生 羊水过多或羊水过少的妊娠小鼠。羊水的变化 膜内微血管密度和VEGF基因与液体体积的关系 表达将是相互关联的。具体目标3将检查胎儿和产后 羊水过多或羊水过少模型中的生长模式，和 探索成年期血压紊乱的发展。整体 假设在怀孕的小鼠中，羊水量的改变 可以通过VEGF基因的遗传操作来诱导，从而产生模型 治疗羊水过多和羊水过少这项研究是一项创新的 了解羊水量调节的方法。模型 羊水过多和羊水过少允许检查胎儿和产后 由于羊水量异常导致的生长和发育缺陷， 子宫。这些研究的结果对于诊断和 治疗妊娠期羊水量失调。

DESCRIPTION (provided by applicant): A comprehensive understanding of the control of amniotic fluid volume is of major clinical importance. We have previously identified a vascular pathway within the fetal membranes for the transfer of fluid from the amniotic compartment into the fetal blood. This pathway is constituted by a network of microvessels on the surface of the placenta and, in sheep, within the amnion and chorion as well. We hypothesize that vascular endothelial growth factor (VEGF) is the determining factor for the absorptive capacity of this intramembranous pathway, thus an important regulator of amniotic fluid volume. In the present application, we propose to develop a mouse model of polyhydramnios and oligohydramnios. The model will be generated using targeted suppression or induction of VEGF gene expression in the fetal membranes and placenta. The advantage of the mouse model is that, it allows the study of the role of VEGF in intramembranous absorption by genetic manipulation. Three specific aims are proposed. Specific Aim 1 proposes to produce polyhydramnios by suppression of VEGF gene expression using a VEGE antisense sequence and oligohydramnios by over-expression of VEGF in the fetal membranes and placenta. Abnormalities in fetal lung development due to amniotic fluid volume changes will be studied. Specific Aim 2 will investigate the proliferation of microvessels in the amnion, chorion and placenta of pregnant mice with polyhydramnios or oligohydramnios. The change in amniotic fluid volume in relation to intramembranous microvessel density and VEGF gene expression will be correlated. Specific Aim 3 will examine fetal and postnatal growth patterns in the polyhydramniotic or oligohydramniotic models, and explore the development of blood pressure disorders in adulthood. The overall hypothesis is that in the pregnant mouse, alterations in amniotic fluid volume can be induced by genetic manipulation of the VEGF gene thus generating models for polyhydramnios and oligohydramnios. The proposed study is an innovative approach to understanding amniotic fluid volume regulation. The models of polyhydramnios and oligohydramnios allow investigation of fetal and postnatal growth and developmental defects due to abnormal amniotic fluid volume in utero. Results from these studies will be important for diagnosis and treatment of amniotic fluid volume disorders during pregnancy.