Song Q, Chao J, Chao L
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
Clin Exp Hypertens. 1996 Nov;18(8):975-93. doi: 10.3109/10641969609081030.
We established a unique transgenic mouse model in liver-targeted expression of human tissue kallikrein using a mouse albumin enhancer and promoter. Northern blot analysis and ELISA showed that human tissue kallikrein was predominantly expressed in the liver of transgenic mice and secreted into the circulation at a high level. The transcript was also detected in the kidney, pancreas, salivary gland and heart at a low level by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Systolic blood pressures were measured by the tail-cuff method, all three independent transgenic mouse lines are hypotensive (84.6 +/- 1.0 mmHg, n = 17; 84.5 +/- 1.5 mmHg, n = 9; 83.1 +/- 0.8 mmHg, n = 13, P < 0.01) compared with the control mice (100.9 +/- 0.9 mmHg, n = 17). Administration of aprotinin, a potent tissue kallikrein inhibitor or Hoe 140, a bradykinin receptor antagonist, restored the blood pressure of transgenic mice but had no significant effect on control littermates. These studies show that over-production of tissue kallikrein in the circulation plays a role in blood pressure regulation.
我们利用小鼠白蛋白增强子和启动子建立了一种独特的转基因小鼠模型，用于在肝脏中靶向表达人组织激肽释放酶。Northern印迹分析和酶联免疫吸附测定显示，人组织激肽释放酶主要在转基因小鼠的肝脏中表达，并高水平分泌到循环系统中。通过逆转录-聚合酶链反应及随后的Southern印迹分析，在肾脏、胰腺、唾液腺和心脏中也检测到低水平的转录本。采用尾套法测量收缩压，与对照小鼠（100.9±0.9 mmHg，n = 17）相比，所有三个独立的转基因小鼠品系均为低血压（84.6±1.0 mmHg，n = 17；84.5±1.5 mmHg，n = 9；83.1±0.8 mmHg，n = 13，P < 0.01）。给予抑肽酶（一种有效的组织激肽释放酶抑制剂）或Hoe 140（一种缓激肽受体拮抗剂）可恢复转基因小鼠的血压，但对同窝对照小鼠无显著影响。这些研究表明，循环中组织激肽释放酶的过量产生在血压调节中起作用。
