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一种被提议用于靶向小胶质细胞的腺相关病毒衣壳在前脑兴奋性神经元中指导基因表达。

An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons.

作者信息

Cao Wenhao, Tan Zhiqun, Berackey Bereket T, Nguyen Jason K, Brown Sara R, Du Shiyang, Lin Bin, Ye Qiao, Seiler Magdalene, Holmes Todd C, Xu Xiangmin

机构信息

Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.

Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; Center for Neural Circuit Mapping, University of California, Irvine, Irvine, CA 92697, USA.

出版信息

Cell Rep Methods. 2025 Jun 16;5(6):101054. doi: 10.1016/j.crmeth.2025.101054. Epub 2025 May 21.

DOI:10.1016/j.crmeth.2025.101054
PMID:40403726
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12272241/
Abstract

A newly developed capsid AAV-MG1.2 was reported to mediate specific microglial transduction. However, we find that AAV-MG1.2 actually enables specific genetic access to excitatory neurons in forebrain regions including hippocampal formation and visual cortex but does not confer expression in microglia or astrocytes in vivo. Furthermore, we find that AAV-MG1.2 specifically labels the deep layer of the CA1 pyramidal layer in a titer-dependent manner. We show that AAV-MG1.2-Cre can be used to genetically target excitatory neurons for cell-type-specific neural circuit mapping studies. We also find that AAV-MG1.2 conserves specificity for excitatory neurons in rat hippocampus. Thus, the AAV-MG1.2 presents a useful viral-genetic tool for targeting excitatory neurons in the forebrain across different species.

摘要

据报道,新开发的衣壳AAV-MG1.2可介导特定的小胶质细胞转导。然而,我们发现AAV-MG1.2实际上能够特异性地对包括海马结构和视觉皮层在内的前脑区域的兴奋性神经元进行基因导入,但在体内小胶质细胞或星形胶质细胞中不表达。此外,我们发现AAV-MG1.2以滴度依赖的方式特异性标记CA1锥体层的深层。我们表明,AAV-MG1.2-Cre可用于对兴奋性神经元进行基因靶向,以进行细胞类型特异性神经回路映射研究。我们还发现AAV-MG1.2在大鼠海马中对兴奋性神经元保持特异性。因此,AAV-MG1.2是一种用于跨不同物种靶向前脑兴奋性神经元的有用病毒遗传工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/4ab4c9b207ae/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/dbcc79ff5fe4/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/b3eacdd9ba12/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/0ba23e1baac8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/8c837e2a3d69/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/2672bb2a1d6e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/86b6544e837a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/5824a3be5180/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/4ab4c9b207ae/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/dbcc79ff5fe4/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/b3eacdd9ba12/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/0ba23e1baac8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/8c837e2a3d69/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/2672bb2a1d6e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/86b6544e837a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/5824a3be5180/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5745/12272241/4ab4c9b207ae/gr7.jpg

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本文引用的文献

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让拉蒙·卡哈尔(Ramón y Cajal)感到骄傲:大脑皮层中的细胞身份和多样性的发展。
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