One-step Cre-loxP organism creation by TAx9

Abstract The creation of organisms with Cre-loxP conditional gene recombination systems often faces challenges, particularly when creating the initial (F0) generation with both a Cre recombinase and a DNA site flanked by loxP elements (floxed site). The primary reason is that it is difficult to synt...

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Main Authors: Martin Miguel Casco-Robles, Tomoki Echigoya, Takeaki Shimazaki, Yuri Murakami, Masaya Hirano, Fumiaki Maruo, Seiya Mizuno, Satoru Takahashi, Chikafumi Chiba
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07759-9
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author Martin Miguel Casco-Robles
Tomoki Echigoya
Takeaki Shimazaki
Yuri Murakami
Masaya Hirano
Fumiaki Maruo
Seiya Mizuno
Satoru Takahashi
Chikafumi Chiba
author_facet Martin Miguel Casco-Robles
Tomoki Echigoya
Takeaki Shimazaki
Yuri Murakami
Masaya Hirano
Fumiaki Maruo
Seiya Mizuno
Satoru Takahashi
Chikafumi Chiba
author_sort Martin Miguel Casco-Robles
collection DOAJ
description Abstract The creation of organisms with Cre-loxP conditional gene recombination systems often faces challenges, particularly when creating the initial (F0) generation with both a Cre recombinase and a DNA site flanked by loxP elements (floxed site). The primary reason is that it is difficult to synthesize a single plasmid with both the Cre gene and the floxed site, since Cre-mediated recombination spontaneously occurs when the plasmid is amplified in Escherichia coli bacterial cells. Here, we introduce an artificial nucleic acid sequence TATATATATATATATATA, named TAx9, that enables the integration of both the Cre gene and the floxed site into a single plasmid. TAx9 effectively blocks spontaneous Cre-mediated recombination in E. coli cells. Using this system, we created an F0 generation of transgenic newts and CRISPR-Cas9 knock-in mice with tissue-specific Cre recombination triggered by tamoxifen. TAx9 technology will be a powerful strategy for creating organisms capable of conditional genetic modification in the F0 generation, accelerating various life science research by reducing the time and cost for ultimately establishing and maintaining lines of genetically modified organisms.
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spelling doaj-art-b6931aa2a5234063a35d138ba856b30b2025-08-20T02:59:57ZengNature PortfolioCommunications Biology2399-36422025-03-018111010.1038/s42003-025-07759-9One-step Cre-loxP organism creation by TAx9Martin Miguel Casco-Robles0Tomoki Echigoya1Takeaki Shimazaki2Yuri Murakami3Masaya Hirano4Fumiaki Maruo5Seiya Mizuno6Satoru Takahashi7Chikafumi Chiba8Institute of Life and Environmental Sciences, University of TsukubaGraduate School of Science and Technology, University of TsukubaGraduate School of Life and Environmental Sciences, University of TsukubaGraduate School of Science and Technology, University of TsukubaGraduate School of Science and Technology, University of TsukubaInstitute of Life and Environmental Sciences, University of TsukubaLaboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of TsukubaLaboratory Animal Resource Center in Transborder Medical Research Center, Institute of Medicine, University of TsukubaInstitute of Life and Environmental Sciences, University of TsukubaAbstract The creation of organisms with Cre-loxP conditional gene recombination systems often faces challenges, particularly when creating the initial (F0) generation with both a Cre recombinase and a DNA site flanked by loxP elements (floxed site). The primary reason is that it is difficult to synthesize a single plasmid with both the Cre gene and the floxed site, since Cre-mediated recombination spontaneously occurs when the plasmid is amplified in Escherichia coli bacterial cells. Here, we introduce an artificial nucleic acid sequence TATATATATATATATATA, named TAx9, that enables the integration of both the Cre gene and the floxed site into a single plasmid. TAx9 effectively blocks spontaneous Cre-mediated recombination in E. coli cells. Using this system, we created an F0 generation of transgenic newts and CRISPR-Cas9 knock-in mice with tissue-specific Cre recombination triggered by tamoxifen. TAx9 technology will be a powerful strategy for creating organisms capable of conditional genetic modification in the F0 generation, accelerating various life science research by reducing the time and cost for ultimately establishing and maintaining lines of genetically modified organisms.https://doi.org/10.1038/s42003-025-07759-9
spellingShingle Martin Miguel Casco-Robles
Tomoki Echigoya
Takeaki Shimazaki
Yuri Murakami
Masaya Hirano
Fumiaki Maruo
Seiya Mizuno
Satoru Takahashi
Chikafumi Chiba
One-step Cre-loxP organism creation by TAx9
Communications Biology
title One-step Cre-loxP organism creation by TAx9
title_full One-step Cre-loxP organism creation by TAx9
title_fullStr One-step Cre-loxP organism creation by TAx9
title_full_unstemmed One-step Cre-loxP organism creation by TAx9
title_short One-step Cre-loxP organism creation by TAx9
title_sort one step cre loxp organism creation by tax9
url https://doi.org/10.1038/s42003-025-07759-9
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