apoE_4近交系转基因鼠的高脂血症表现和自发变换行为损害

建立相关疾病的动物模型 ,研究apoE4在脂质代谢和早老性痴呆等疾病中的作用 .通过显微注射法建立人apoE4近交系转基因鼠 .经Southern和Northern印迹杂交 ,鉴定apoE4基因的整合与表达 .98只新生鼠中鉴定出 2只首建鼠 ,定名为TgN(apoE4) 1QiL和TgN(apoE4) 2QiL .外源基因整合的拷贝数分别为 1和 2 .F1代杂合鼠的脑 ,肾脏 ,心脏和肝脏中均有人apoE4基因的表达 .血清脂质水平通过酶法检测 ,自发变换行为经Y迷宫试验检测 .转基因鼠的血清胆固醇和甘油三酯明显升高 ,自发变换行为受到损害 .结果表明 ,近交系转基因鼠过量表达人apoE4基因可导致血清脂质升高 ,并对其空间记忆能力造成损害 .

The Hyperlipidemia and Spontaneous Alternation Behavior Impairment in Human Apolipoprotein E_4 (apoE_4) Inbred Transgenic Mice

To establish an animal model of human disease and investigate the role of apoE 4 in lipoprotein metabolism and Alzheimer′s disease, the human apoE\-4 transgenic mice were generated via microinjection. Southern blot and Northern blot hybridization were used to identify the integration and expression of the transgene, respectively. Enzymatic methods were used to test serum lipids. Y\|maze was used to test the spontaneous alternation behavior. Two founders were detected from 98 newborn mice, the copy numbers were 1 and 2. They were named as TgN(apoE 4)1QiL and TgN(apoE 4)2QiL, respectively. For F 1 heterozygotes, human apoE 4 mRNA can be detected in the brain, kidney, heart and liver, but not in the spleen. Compared with the control, serum cholesterol and triglyceride are also elevated, spontaneous alternation behavior is impaired. The results demonstrate that overexpression of human apoE 4 in inbred transgenic mice increases plasma lipid levels and impairs primitive working memory capacity.