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Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions

Author

Listed:
  • Hyunjin Jung

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Seong-Wook Kim

    (Institute for Basic Science (IBS))

  • Minsoo Kim

    (Institute for Basic Science (IBS))

  • Jongryul Hong

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Daseuli Yu

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Ji Hye Kim

    (Institute for Basic Science (IBS))

  • Yunju Lee

    (Institute for Basic Science (IBS))

  • Sungsoo Kim

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Doyeon Woo

    (Institute for Basic Science (IBS))

  • Hee-Sup Shin

    (Institute for Basic Science (IBS))

  • Byung Ouk Park

    (Institute for Basic Science (IBS))

  • Won Do Heo

    (Korea Advanced Institute of Science and Technology (KAIST)
    Institute for Basic Science (IBS)
    KAIST Institute for the BioCentury, KAIST)

Abstract

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 Cav3.1 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.

Suggested Citation

  • Hyunjin Jung & Seong-Wook Kim & Minsoo Kim & Jongryul Hong & Daseuli Yu & Ji Hye Kim & Yunju Lee & Sungsoo Kim & Doyeon Woo & Hee-Sup Shin & Byung Ouk Park & Won Do Heo, 2019. "Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08282-8
    DOI: 10.1038/s41467-018-08282-8
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    Cited by:

    1. Deqiang Kong & Yang Zhou & Yu Wei & Xinyi Wang & Qin Huang & Xianyun Gao & Hang Wan & Mengyao Liu & Liping Kang & Guiling Yu & Jianli Yin & Ningzi Guan & Haifeng Ye, 2024. "Exploring plant-derived phytochrome chaperone proteins for light-switchable transcriptional regulation in mammals," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Catarina Rebelo & Tiago Reis & Joana Guedes & Cláudia Saraiva & Artur Filipe Rodrigues & Susana Simões & Liliana Bernardino & João Peça & Sónia L. C. Pinho & Lino Ferreira, 2022. "Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Charlotte Cautereels & Jolien Smets & Jonas De Saeger & Lloyd Cool & Yanmei Zhu & Anna Zimmermann & Jan Steensels & Anton Gorkovskiy & Thomas B. Jacobs & Kevin J. Verstrepen, 2024. "Orthogonal LoxPsym sites allow multiplexed site-specific recombination in prokaryotic and eukaryotic hosts," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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