ANALYSIS OF ACE KNOCKOUT MICE

血管紧张素转换酶(ACE)是一种羧基肽酶 将不活跃的前体血管紧张素I转化为血管紧张素II。ACE是关键 肾素-血管紧张素系统(RAS)的组成部分，起着非常重要的作用 在生理上控制血压和液体平衡。生理学 RSA的操作比简单的血压控制更复杂，因为 缺乏功能性基因的基因敲除小鼠的表型证明 肾素-血管紧张素系统。在这笔赠款的头四年里，这群人 创造并研究了缺乏血管紧张素转换酶的老鼠。这些动物体内的脂肪含量很低 收缩压，各种肾脏异常，贫血，和 生殖异常。这项竞争性申请是为了继续 对这些动物的研究旨在通过以下方式了解其机制 RAS对正常和异常生理的影响。具体地说， 拟议的实验旨在研究1)RAS在流体中的作用 以及ACE基因敲除小鼠出现的血液学异常，2) RAS在肾脏浓缩机制中的作用，以及3)局部、 血管紧张素转换酶在心血管功能调节中的组织特异性表达

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.