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

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 bi...

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Vydáno v:	Nature communications Ročník 13; číslo 1; s. 6442 - 15
Hlavní autoři:	Vizoso, Miguel, E. J. Pritchard, Colin, Bombardelli, Lorenzo, van den Broek, Bram, Krimpenfort, Paul, Beijersbergen, Roderick L., Jalink, Kees, van Rheenen, Jacco
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 28.10.2022 Nature Publishing Group Nature Portfolio
Témata:	13/1 13/106 13/107 13/109 13/31 13/44 13/51 14 14/1 14/19 14/69 38 59 631/1647/2253 631/1647/334/1874/345 631/61/17/1511 631/67/2321 64 64/60 Animals Antibiotics Biomedical engineering Biomedical materials Biomedical research Cre recombinase Dermis Doxycycline Doxycycline - pharmacology Editing Engineers Gene Editing Gene expression Genome editing Genomes Humanities and Social Sciences Integrases - genetics Integrases - metabolism Medical research Mice Mice, Inbred Strains Mice, Transgenic multidisciplinary Mutagenesis Optogenetics Organoids Recombination Science Science (multidisciplinary) Tracing
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. Achieving spatial control of gene expression is important. Here the authors report an optimised photoactivatable Cre recombinase system, doxycycline- and light-inducible Cre recombinase (DiLiCre), and generate a DiLiCre mouse line which they use for mutagenesis in vivo and positional cell-tracing.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-022-33863-z