Sheng H, Laskowitz D T, Bennett E, Schmechel D E, Bart R D, Saunders A M, Pearlstein R D, Roses A D, Warner D S
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Cereb Blood Flow Metab. 1998 Apr;18(4):361-6. doi: 10.1097/00004647-199804000-00003.
Apolipoprotein E (apoE), a 34-KD glycosylated lipid-binding protein, is expressed as three common isoforms in humans (E2, E3, or E4). Clinical evidence suggests that the apoE genotype (APOE) may be a risk factor for poor outcome after acute central nervous system injury. This was examined further in transgenic mice constructed with the human APOE3 or APOE4 gene under the control of human promoter and tissue expression elements. Presence of human apoE3 and apoE4 proteins in brains of human APOE homozygous transgenic mice was confirmed by Western blotting. APOE3 (n = 12) and APOE4 (n = 10) mice underwent 60 minutes of middle cerebral artery occlusion. After 24-hour recovery, infarct size was measured. Infarct volumes (mean +/- standard deviation) were smaller in the APOE3 group (cortex: APOE3 = 18 +/- 4 mm3; APOE4 = 30 +/- 11 mm3, P = 0.04; subcortex: APOE3 = 12 +/- 4 mm3; APOE4 = 18 +/- 4 mm3, P = 0.003). Hemiparesis was less severe in APOE3 mice (P = 0.02). These data indicate that human isoform-specific effects of apoE are relevant to acute pathomechanisms of focal ischemic brain damage when examined in the mouse. APOE transgenic mice may provide an appropriate model to examine the mechanistic basis for the differential effects of human apoE isoforms in acute central nervous system injury.
载脂蛋白E（apoE）是一种34千道尔顿的糖基化脂质结合蛋白，在人类中以三种常见异构体（E2、E3或E4）形式表达。临床证据表明，apoE基因型（APOE）可能是急性中枢神经系统损伤后预后不良的一个风险因素。在用人类启动子和组织表达元件控制下构建的携带人类APOE3或APOE4基因的转基因小鼠中对此进行了进一步研究。通过蛋白质免疫印迹法证实了人类APOE纯合转基因小鼠大脑中存在人类apoE3和apoE4蛋白。APOE3（n = 12）和APOE4（n = 10）小鼠接受了60分钟的大脑中动脉闭塞。恢复24小时后，测量梗死面积。APOE3组的梗死体积（平均值±标准差）较小（皮层：APOE3 = 18±4立方毫米；APOE4 = 30±11立方毫米，P = 0.04；皮层下：APOE3 = 12±4立方毫米；APOE4 = 18±4立方毫米，P = 0.003）。APOE3小鼠的偏瘫症状较轻（P = 0.02）。这些数据表明，在小鼠中进行研究时，apoE的人类异构体特异性效应与局灶性缺血性脑损伤的急性发病机制相关。APOE转基因小鼠可能为研究人类apoE异构体在急性中枢神经系统损伤中差异效应的机制基础提供一个合适的模型。
