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Lentiviruses allow widespread and conditional manipulation of gene expression in the developing mouse brain

Authors :
Federico Calegari
Benedetta Artegiani
Source :
Development. 140:2818-2822
Publication Year :
2013
Publisher :
The Company of Biologists, 2013.

Abstract

Generation of transgenic mice, in utero electroporation and viral injection are common approaches to manipulate gene expression during embryonic development of the mammalian brain. While very powerful in many contexts, these approaches are each characterized by their own limitations: namely, that generation of transgenic mice is time-consuming and electroporation only allows the targeting of a small area of the brain. Similarly, viral injection has been predominantly characterized by using retroviruses or adenoviruses that are limited by a relatively low infectivity or lack of integration, respectively. Here we report the use of integrating lentiviral vectors as a system to achieve widespread and efficient infection of the whole brain after in utero injection in the telencephalic ventricle of mouse embryos. In addition, we explored the use of Cre-mediated recombination of loxP-containing lentiviral vectors to achieve spatial and temporal control of gene expression of virtually any transgene without the need for generation of additional mouse lines. Our work provides a system to overcome the limitations of retroviruses and adenoviruses by achieving widespread and high efficiency of transduction. The combination of lentiviral injection and site-specific recombination offers a fast and efficient alternative to complement and diversify the current methodologies to acutely manipulate gene expression in developing mammalian embryos.

Details

ISSN :
14779129 and 09501991
Volume :
140
Database :
OpenAIRE
Journal :
Development
Accession number :
edsair.doi.dedup.....0da9b95a1bc1e58f84b87cb6d57d6acd
Full Text :
https://doi.org/10.1242/dev.093823