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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Vydané v:Nature communications Ročník 13; číslo 1; s. 6442 - 15
Hlavní autori: 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:English
Vydavateľské údaje: London Nature Publishing Group UK 28.10.2022
Nature Publishing Group
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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
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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.
Bibliografia:ObjectType-Article-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33863-z