SOD_1基因突变子对AD转基因小鼠β-淀粉样蛋白表达影响的实验研究

Effect of Muntant SOD_1 on the Expression of the Aβ Peptide of Alzheimer's Disease in a Double-transgenic Mice

目的 :探讨Cu/ZnSOD1基因表达对Aβ产生的影响。 方法 :建立APP C10 0和G93ASOD1基因共表达的转双基因小鼠 ,应用免疫细胞化学方法测定不同鼠龄转基因鼠海马神经元Aβ表达 ,Westernblot定量测定转基因鼠脑SOD1、APP、APP C10 0和Aβ表达水平。结果 :低龄转双基因鼠与转单基因鼠之间Aβ水平无差异 ,与年龄匹配的转单基因鼠比较 ,高龄转双基因鼠脑Aβ水平升高 ,经统计处理差异无显著性意义 (P >0 0 5 )。但高龄转双基因鼠Aβ水平比低龄转双基因鼠明显升高 (P <0 0 5 )。 结论 :转双基因鼠脑APP C10 0和G93ASOD1基因共表达虽然未导致老年斑形成 ,但引起Aβ含量增加 。

Aim:To explore the effect of coexpression of APP-C100 and G93A SOD 1 gene in vivo on the beta-amyloid production.Methods:The double transgenic mice coexpressing the human APP-C100 and G93A SOD 1 gene was generated by cross-breeding.Immunocytochemistry was used to detect the Aβ levels in hippocampus with young (2-3 months) and aged (8-9 months) transgenic mice.The levels of SOD 1,APP,APP-C100 and Aβ of four genotype mice were quantitated by Western Blot.Results:There was no difference between young double transgenic mice and single transgenic mice expressing APP-C100 gene alone.The Aβ level of aged double transgenic mice was increased compared to that of age-matched single transgenic mice,but non-significant difference was found.Compared with young double transgenic mice,the aged double transgenic mice showed a significant increase in Aβ level.Conclusion:The coexpression of APP-C100 and G93A SOD 1 gene in double transgenic mice did not produce extracellular senile plaque,but increased Aβ level,this alteration may relate to the oxidative stress induced by mutant SOD 1.