Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Cerebellum. 2012 Jun;11(2):443-5. doi: 10.1007/s12311-011-0330-x.
Postmitotic neurons are resistant to gene delivery. However, lentiviral vectors allow the introduction of a foreign gene efficiently into neurons without significant toxicity to the infected cells (Sawada et al., Cerebellum 9(3):291-302, 2010). In addition, these vectors show a high tropism for neurons, and the transgenes they carry have been shown to be continuously expressed for at least a couple of years (Hirai, Cerebellum 7(3):273-8, 2008). We developed a method to express a foreign gene efficiently in cerebellar Purkinje cells in vivo (Takayama et al., Neurosci Lett 443(1):7-11, 2008; Torashima et al., Brain Res 1082(1):11-22, 2006, The Eur J Neurosci 24(2):371-80, 2006). Using our method, various experiments were carried out to study the pathophysiology of the cerebellum, including the investigation of a cerebellum-specific gene of unknown function, the generation and analysis of a mouse model of the spinocerebellar ataxia, and the rescue of an ataxic phenotype in mutant mice by introducing a defective gene or a therapeutic gene into the Purkinje cells. Here, we introduce our recent studies on expressing transgenes in the cerebellum using lentiviral vectors.
已分化神经元对基因传递具有抗性。然而，慢病毒载体可以高效地将外源基因导入神经元，而对感染细胞的毒性较小（Sawada 等人，小脑 9(3):291-302, 2010）。此外，这些载体对神经元具有高亲嗜性，并且它们携带的转基因至少可以持续表达几年（Hirai，小脑 7(3):273-8, 2008）。我们开发了一种在体内高效表达小脑浦肯野细胞中外源基因的方法（Takayama 等人，神经科学快报 443(1):7-11, 2008；Torashima 等人，脑研究 1082(1):11-22, 2006，欧洲神经科学杂志 24(2):371-80, 2006）。使用我们的方法，进行了各种实验来研究小脑的病理生理学，包括对未知功能的小脑特异性基因的研究、脊髓小脑共济失调模型的产生和分析，以及通过将缺陷基因或治疗基因引入浦肯野细胞来挽救突变小鼠的共济失调表型。在这里，我们介绍了我们最近使用慢病毒载体在小脑中转基因表达的研究。
