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A doxycycline- and light-inducible Cre recombinase mouse model for optogenetic genome editing

Author

Listed:
  • Miguel Vizoso

    (Oncode Institute, Netherlands Cancer Institute)

  • Colin E. J. Pritchard

    (The Netherlands Cancer Institute)

  • Lorenzo Bombardelli

    (Netherlands Cancer Institute)

  • Bram van den Broek

    (The Netherlands Cancer Institute
    BioImaging Facility, The Netherlands Cancer Institute)

  • Paul Krimpenfort

    (The Netherlands Cancer Institute)

  • Roderick L. Beijersbergen

    (Netherlands Cancer Institute
    The Netherlands Cancer Institute)

  • Kees Jalink

    (The Netherlands Cancer Institute
    University of Amsterdam)

  • Jacco van Rheenen

    (Oncode Institute, Netherlands Cancer Institute)

Abstract

The experimental need to engineer the genome both in time and space, has led to the development of several photoactivatable Cre recombinase systems. However, the combination of inefficient and non-intentional background recombination has prevented thus far the wide application of these systems in biological and biomedical research. Here, we engineer an optimized photoactivatable Cre recombinase system that we refer to as doxycycline- and light-inducible Cre recombinase (DiLiCre). Following extensive characterization in cancer cell and organoid systems, we generate a DiLiCre mouse line, and illustrated the biological applicability of DiLiCre for light-induced mutagenesis in vivo and positional cell-tracing by intravital microscopy. These experiments illustrate how newly formed HrasV12 mutant cells follow an unnatural movement towards the interfollicular dermis. Together, we develop an efficient photoactivatable Cre recombinase mouse model and illustrate how this model is a powerful genome-editing tool for biological and biomedical research.

Suggested Citation

  • Miguel Vizoso & Colin E. J. Pritchard & Lorenzo Bombardelli & Bram van den Broek & Paul Krimpenfort & Roderick L. Beijersbergen & Kees Jalink & Jacco van Rheenen, 2022. "A doxycycline- and light-inducible Cre recombinase mouse model for optogenetic genome editing," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33863-z
    DOI: 10.1038/s41467-022-33863-z
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    References listed on IDEAS

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    1. Fuun Kawano & Hideyuki Suzuki & Akihiro Furuya & Moritoshi Sato, 2015. "Engineered pairs of distinct photoswitches for optogenetic control of cellular proteins," Nature Communications, Nature, vol. 6(1), pages 1-8, May.
    2. Kumi Morikawa & Kazuhiro Furuhashi & Carmen Sena-Tomas & Alvaro L. Garcia-Garcia & Ramsey Bekdash & Alison D. Klein & Nicholas Gallerani & Hannah E. Yamamoto & Seon-Hye E. Park & Grant S. Collins & Fu, 2020. "Photoactivatable Cre recombinase 3.0 for in vivo mouse applications," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. Stefano Annunziato & Julian R. de Ruiter & Linda Henneman & Chiara S. Brambillasca & Catrin Lutz & François Vaillant & Federica Ferrante & Anne Paulien Drenth & Eline van der Burg & Bjørn Siteur & Bas, 2019. "Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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    1. 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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