Targeted ectopic expression of genes in the adult brain is an invaluable approach for studying many biological processes. This can be accomplished by generating transgenic mice or by virally mediated gene transfer, but these methods are costly and labor intensive. We devised a rapid strategy that allows localized in vivo transfection of plasmid DNA within the adult neurogenic niches without detectable brain damage. Injection of plasmid DNA into the ventricular system or directly into the hippocampus of adult mice, followed by application of electrical current via external electrodes, resulted in transfection of neural stem or progenitor cells and mature neurons. We showed that this strategy can be used for both fate mapping and gain- or loss-of-function experiments. Using this approach, we identified an essential role for cadherins in maintaining the integrity of the lateral ventricle wall. Thus, in vivo electroporation provides a new approach to study the adult brain.
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We thank R. Kageyama (Kyoto University) for the gift of the nestin promoter vector30, C. Ibáñez (Karolinska Institutet) for the gift of a BDNF expression plasmid, M. Wheelock (University of Nebraska Medical Center) for providing the dominant-negative N-cadherin cDNA and K. Fernandes (University of Montreal) for critically reading the manuscript. This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Foundation for Strategic Research, the Karolinska Institutet, Tobias Stiftelsen and the European Commission Framework VI Programme, EuroStemCell. F.B.-H. is supported by a postdoctoral fellowship from Canadian Institutes of Health Research.
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Barnabé-Heider, F., Meletis, K., Eriksson, M. et al. Genetic manipulation of adult mouse neurogenic niches by in vivo electroporation. Nat Methods 5, 189–196 (2008). https://doi.org/10.1038/nmeth.1174
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