体内GRK5缺陷加剧Tg2576小鼠海马内的病理改变

GRK5 DEFICIENCY EXAGGERATES HIPPOCAMPAL PATHOLOGICAL CHANGES IN TG2576 MICE

目的研究体内G蛋白偶联受体激酶5(GRK5)缺陷是否会加剧转瑞典突变淀粉样肽前体蛋白基因(TgAPPsw,Tg2576)小鼠海马内的病理改变。方法将具有C57/BL6遗传背景的GRK5缺陷/敲除(GRK5KO)杂合子与具有相同遗传背景的Tg2576小鼠杂交,以产生野生型(WT)、GRK5KO杂合子型、转淀粉样肽前体蛋白(APP)基因型以及转基因&敲除(Double)型4种基因型小鼠。用免疫荧光(IF)染色方法来观察这些动物海马内肿胀轴突丛(SACs)和Aβ沉积量变化。结果IF染色结果定量分析显示,Tg2576小鼠被灭活一个拷贝的GRK5基因后导致海马内SACs和Aβ沉积量均显著增加。结论体内GRK5缺陷加剧了AD动物海马内的病理改变。

Objective To determine whether deficiency of membrane G-protein coupled receptor （GPCR） kinase-5 （GRK5） in vivo exaggerates hippocampal pathological changes in TgAPPsw （Tg2576） mice. Methods The heterozygotes of GRK5 knockout/deficiency （GRKSKO） mice with a C57/BL6 background were bred with Tg2576 mice also with a C57/BL6 background to produce wild type （WT）, GRK5KO, amyloid precursor protein （APP） and the double mice for this study. Both quantitative and qualitative immunofluorescent （IF） staining methods were used to evaluate the swollen axonal clusters （SACs） and β-amyloid （Aβ） deposition in these mice. Results Inactivation of one copy of the GRK5 gene in the Tg2576 mice resulted in a significant increase of SACs and Aβ plaque deposits in hippocampus of the aged animals. Conclusion The results demonstrate that knockdown GRK5 gene by 50% in the Tg2576 mice significantly exaggerates the hipocampal pathological changes of these animals.