ANALYSIS OF ACE KNOCKOUT MICE

血管紧张素转换酶（ACE）是一种羧基肽酶， 将无活性的前体血管紧张素I转化为血管紧张素II。ACE是一把钥匙 血管紧张素是肾素-血管紧张素系统（RAS）的一个重要组成部分， 在血压和体液平衡的生理控制方面。生理 RSA的作用比简单的血压控制更复杂， 通过敲除小鼠的表型证明， 血管紧张素系统在这项资助的前四年， 已经创造并研究了缺乏ACE的小鼠。这些动物有很低的 收缩压，各种肾脏异常，贫血， 生殖异常这项竞争性的申请是为了继续 研究这些动物的目的是了解机制， RAS影响正常和异常的生理。具体而言是 建议的实验设计研究1）RAS在流体中的作用 ACE基因敲除小鼠中存在的血液学异常，2） RAS在肾浓缩机制中的作用，以及3）局部， ACE的组织特异性表达在调节心血管功能中的作用。

Angiotensin converting enzyme (ACE) is a carboxyl peptidase that converts the inactive precursor angiotensin I into angiotensin II. ACE is a key component of the renin-angiotensin system (RAS) and plays a very important role in the physiologic control of blood pressure and fluid balance. The physiologic actions of the RSA are more complex than simple blood pressure control, as evidenced by the phenotype of knockout mice that lack a functional renin-angiotensin system. During the first four years of this grant, this group has created and studied mice that lack ACE. These animals have very low systolic blood pressures, a variety of renal abnormalities, anemia, and reproductive abnormalities. This competitive application is to continue the study of these animals towards the goal of understanding the mechanisms by which the RAS influences normal and abnormal physiology. Specifically, the proposed experiments are designed to study 1) the role of the RAS in the fluid and hematological abnormalities present in ACE knockout mice, 2) the role of the RAS in the renal concentrating mechanism, and 3) the role of the local, tissue specific expression of ACE in regulating cardiovascular function.