Adeno-associated virus effectively mediates conditional gene modification in the brain
Adeno-associated virus effectively mediates conditional gene modification in the brain
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DOI：
10.1073/pnas.042678699
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发表时间：
2002-02-19
影响因子：
11.1
通讯作者：
Gage, FH
中科院分区：
文献类型：
--
作者：
Kaspar, BK;Vissel, B;Gage, FH
Cre/loxP系统在研究与神经功能有关的基因方面越来越有前景。在这里，我们证明，通过靶向递送编码绿色荧光蛋白/Cre重组酶（GFP/Cre）融合蛋白的腺相关病毒（AAV），可以以空间和时间特异性的方式完成小鼠大脑中基因的体内修饰。通过使用Cre重组酶激活β -半乳糖苷酶表达的报告小鼠，我们证实早在立体定向注射病毒后7天，海马、纹状体和隔区神经元就出现了长期重组。注射后至少6个月观察到重组细胞，没有细胞丢失或神经损伤的证据。AAV介导的GFP/Cre递送为改变小鼠基因组提供了一种有价值的方法，因为AAV以低毒性有效地将基因递送到神经元。这种方法将极大地促进小鼠大脑遗传修饰的研究。
The Cre/loxP system is increasingly showing promise for investigating genes involved in neural function. Here, we demonstrate that in vivo modification of genes in the mouse brain can be accomplished in a spatial- and temporal-specific manner by targeted delivery of an adeno-associated virus (AAV) encoding a green fluorescent protein/Cre recombinase (GFP/Cre) fusion protein. By using a reporter mouse, in which Cre recombinase activates beta-galactosidase expression, we demonstrate long-term recombination of neurons in the hippocampus, striatum, and septum as early as 7 days after stereotaxic injection of virus. Recombined cells were observed for at least 6 months postinjection without evidence of cell loss or neural damage. AAV-mediated delivery of GFP/Cre provides a valuable approach to alter the mouse genome, as AAV delivers genes efficiently to neurons with low toxicity. This approach will greatly facilitate the study of genetic modifications in the mouse brain.