Song Q, Chao J, Chao L
Department of Biochemistry and Molecular Biology Medical University of South Carolina, Charleston 29425, USA.
Immunopharmacology. 1996 May;32(1-3):105-7. doi: 10.1016/0162-3109(95)00065-8.
In order to create an animal model expressing a high level of tissue kallikrein in the circulation, the human tissue kallikrein gene was placed under the control of a mouse albumin enhancer and promoter to target its expression to liver. Three lines of transgenic mice carrying the human tissue kallikrein gene were established. The major site of human tissue kallikrein synthesis was identified in the liver of transgenic mice, and a high level of human tissue kallikrein was secreted into the mouse circulation. The systolic blood pressures of these transgenic mice are about 15-20 mmHg lower than that of the control mice. Administration of aprotinin, a potent tissue kallikrein inhibitor, restored normal blood pressure in these animals. These studies show that a high level of foreign tissue kallikrein in the circulation plays a role in blood pressure regulation.
为了创建一种在循环系统中高水平表达组织激肽释放酶的动物模型，将人类组织激肽释放酶基因置于小鼠白蛋白增强子和启动子的控制之下，使其表达定位于肝脏。建立了携带人类组织激肽释放酶基因的三系转基因小鼠。在转基因小鼠的肝脏中确定了人类组织激肽释放酶的主要合成部位，并且有高水平的人类组织激肽释放酶分泌到小鼠循环系统中。这些转基因小鼠的收缩压比对照小鼠低约15 - 20 mmHg。给予抑肽酶（一种有效的组织激肽释放酶抑制剂）可使这些动物的血压恢复正常。这些研究表明，循环系统中高水平的外源组织激肽释放酶在血压调节中起作用。
