构建了两种新的重组人泡沫病毒载体pGPSNI—hGAD67和pGPSNI—hGAD65,分别携带人符氨酸脱羧酶(GAD)的两种同工酶GAD65和GAD67基因,并研究其在帕金森病(PD)模刭鼠丘脑底核中的表达及对帕金森病的治疗作用.RT—PCR结果表明,人泡沫病毒载体成功地介导了GAD65基因和GAD67基因在PD模型鼠丘脑底核中有效表达.动物行为检测表明,GAD65基因导入组PD模型鼠行为与对照组相比得到明显的改善(n=12,由〈0.01).
In this study, two novel replication-defective human foamy virus (HFV) vectors plasmids pGPSNI-hGAD67 and pGPSNI-hGAD65 were constructed and contain two transcription units: one enco ding the neomycine phosphotransferase gene and the other encoding a single human glutamic acid decarboxylase (GAD) isoforms (hGAD67 or hGAD65). Furthermore, the GAD gene mediated by HFV was trans duced in excitatory glutamatergic neurons of the subthalamic nucleus (STN) of Parkinson's Disease (PD) rats, so that the gene transcription and expression and the theraputic effect on PD rats models was observed. The results of RT PCR suggest that effective foreign genes were expressed in the STN of PD ra, ts by successful GAD65 or GAD67 gene transduction through a HFV vector mediating GAD gene. To determine animal behavior, we found that PD rats received C-AD65 gene treatment revealed decreasing rotation (n=12, p〈0.01).