摘要
目的 研究突变的人载脂蛋白 E(apo E)对大脑皮层功能的影响。方法 以 F1代 apo E4与 apo E7转基因小鼠为研究对象 ,分别用 Southern印迹分析及 EL ISA检测人 apo E基因在 F1代小鼠染色体上的整合与在血中的表达 ;以主动回避实验检测小鼠的学习能力和短期与长期记忆能力的变化 ,同时用酶法测定 F1代小鼠的血脂水平。结果 (1)人 apo E4和 apo E7基因稳定地整合于 F1代小鼠染色体上并高效表达于血清中 ;(2 ) F1代小鼠血脂升高的同时 ,apo E4小鼠学习能力与短期记忆能力均显著下降 ,apo E7小鼠短期记忆能力也下降。结论 人apo E4与 apo E7基因过度表达均可使转基因小鼠大脑皮层功能受损害 ,提示人 apo E基因突变可能与 apo E4表型一样 ,也与早老性痴呆的发病有一定关系。
Objective To study the influences of the mutants of human apolipoprotein E on the function of cerebral cortex. Methods The Southern blot hybridization and ELISA techniques were used for identification of integration and expression of human apoE4 and apoE7 genes at the mice chromosome and in the serum of F1 transgenic mice. Then the active avoidance response test was performed to determine the alteration of learning and short term and long term memory of the transgenic mice. The serum total cholesterol (TC) and triglyceride (TG) were determined simultaneously with enzymatic procedure. Results (1) In F1 transgenic mice the human apoE genes integrated at the chromosome and expressed in their serum stably.(2) In apoE4 mice the learning and short term memorizing abilities were decreased, and in apoE7 mice the short term memorizing abilities were decreased as well. In addition, the TC and TG increased statistically. Conclusions The overexpression of human apoE4 and apoE7 genes in transgenic mice could damage the function of cerebral cortex. It denoted that the mutations of apoE might correlate the pathogenesis of Alzheimer′s disease.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2000年第4期348-351,共4页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金!( 3 9470 2 3 4 )资助&&
关键词
载脂蛋白E
转基因小鼠
学习
记忆
human apolipoprotein E
transgenic mice
learning
memorizing
