MOLECULAR GENETICS OF MUSCLE SPECIALIZATION: CARDIAC FUNCTION

肌红蛋白，一种在心脏中表达的细胞内血红素蛋白， 脊椎动物的氧化骨骼肌纤维，结合分子氧 并且已经提出促进氧从红细胞的运输 线粒体，从而维持细胞呼吸， 生理需求旺盛的时期。 我们制造了转基因小鼠 通过基因敲除技术缺失肌红蛋白， 等位基因到纯合性。 心脏和比目鱼肌 是脱色的，但没有肌红蛋白的小鼠是有生育能力的， 正常的运动能力和对 缺氧 这些数据表明，肌红蛋白不是必需的， 满足怀孕或运动的代谢要求， 陆地哺乳动物，并提出了关于氧气的新问题 运输和代谢的调节。 以确定 如果肌红蛋白的丢失调节了对缺血的反应， 再灌注，我们最近开始研究分离的 工作小鼠心脏制备。 低流量缺血是由 显著降低主动脉灌注压， 灌注压 使用31P NMR，ATP，PCr，Pi和pH被 在30天之前、期间和之后在工作小鼠心脏中测量 缺血10分钟，恢复60分钟， 测量机械性能和肌酸激酶释放。 的 这项研究的结果正在评估中。 （服务14）报告 （1997年9月1日至1998年8月31日）

Myoglobin, an intracellular hemoprotein expressed in the heart and oxidative skeletal myofibers of vertebrates, binds molecular oxygen and has been proposed to facilitate oxygen transport from erythrocytes to mitochondria, thereby maintaining cellular respiration during periods of high physiological demand. We generated transgenic mice lacking myoglobin by gene knockout technology and breeding the null allele to homozygosity. Heart and soleus muscles from these animals are depigmented, but mice without myoglobin are fertile and exhibit both normal exercise capacity and a normal ventilatory response to hypoxia. These data demonstrate that myoglobin is not essential to meet the metabolic requirements of pregnancy or exercise in a terrestrial mammal, and raise new questions with respect to oxygen transport and metabolic regulation in working muscles. To determine if loss of myoglobin modulates the response to ischemia and reperfusion, we have recently initiated studies of the isolated working mouse heart preparation. Low flow ischemia is induced by markedly reducing aortic perfusion pressure which reduces coronary perfusion pressure. Using 31P NMR, ATP, PCr, Pi and pH are being measured in the working mouse heart before, during and after 30 minutes of ischemia and 60 minutes of recovery with complementary measures of mechanical performance and creatine kinase release. The results from this study are under evaluation. (Service 14) REPORT PERIOD: (09/01/97-08/31/98)