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Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions
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Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions
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Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions
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Journal Article
Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions
2019
Overview
Spatiotemporal control of gene expression or labeling is a valuable strategy for identifying functions of genes within complex neural circuits. Here, we develop a highly light-sensitive and efficient photoactivatable Flp recombinase (PA-Flp) that is suitable for genetic manipulation in vivo. The highly light-sensitive property of PA-Flp is ideal for activation in deep mouse brain regions by illumination with a noninvasive light-emitting diode. In addition, PA-Flp can be extended to the Cre-lox system through a viral vector as Flp-dependent Cre expression platform, thereby activating both Flp and Cre. Finally, we demonstrate that PA-Flp–dependent, Cre-mediated Ca
v
3.1 silencing in the medial septum increases object-exploration behavior in mice. Thus, PA-Flp is a noninvasive, highly efficient, and easy-to-use optogenetic module that offers a side-effect-free and expandable genetic manipulation tool for neuroscience research.
Most approaches to control gene expression in vivo require generation of knock-in mouse lines and often lack spatiotemporal control. Here the authors develop a photo-activatable Flp recombinase system and demonstrate its use by controlling object-exploration behavior in mice through Cav3.1 silencing.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 38
/ 42/35
/ 42/41
/ 42/44
/ 64
/ 64/60
/ 82/51
/ Animals
/ Behavior, Animal - physiology
/ Brain
/ Calcium channels (voltage-gated)
/ Calcium Channels, T-Type - genetics
/ Calcium Channels, T-Type - metabolism
/ DNA Nucleotidyltransferases - genetics
/ DNA Nucleotidyltransferases - metabolism
/ DNA Nucleotidyltransferases - radiation effects
/ Humanities and Social Sciences
/ Humans
/ Light
/ Science
/ Septum
