iSuRe-Cre is a genetic tool to reliably induce and report Cre-dependent genetic modifications

Abstract

Most biomedical research aimed at understanding gene function uses the Cre-Lox system, which consists of the Cre recombinase-dependent deletion of genes containing LoxP sites. This system enables conditional genetic modifications because the expression and activity of the recombinase Cre/CreERT2 can be regulated in space by tissue-specific promoters and in time by the ligand tamoxifen. Since the precise Cre-Lox recombination event is invisible, methods were developed to report Cre activity and are widely used. However, numerous studies have shown that expression of a given Cre activity reporter cannot be assumed to indicate deletion of other LoxP-flanked genes of interest. Here, we report the generation of an inducible dual reporter-Cre mouse allele, iSuRe-Cre. By significantly increasing Cre activity in reporter-expressing cells, iSuRe-Cre provides certainty that these cells have completely recombined floxed alleles. This genetic tool increases the ease, efficiency, and reliability of conditional mutagenesis and gene function analysis.

Abstract

The Cre-Lox system allows high spatiotemporal control of genetic modifications. Here the authors present iSuRe-Cre that significantly increases Cre activity in reporter expressing cells, which ultimately increases the efficiency and reliability of Cre-dependent reporter and gene function analysis.

Contributors

Rui Benedito:

ORCID: http://orcid.org/0000-0003-2458-3055

[e-mail]

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 22 May 2019

Publication date PMC-release: 22 May 2019

Publication date Collection: 2019

Volume: 10

Affiliations

ISNI 0000 0001 0125 7682, GRID grid.467824.b, Molecular Genetics of Angiogenesis Group, , Centro Nacional de Investigaciones Cardiovasculares (CNIC), ; Madrid, E28029 Spain

Article

Publisher ID: 10239

DOI: 10.1038/s41467-019-10239-4

PMC ID: 6531465

PubMed ID: 31118412

Copyright statement: © The Author(s) 2019

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Funding

Funded by: FundRef https://doi.org/10.13039/100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);

Categories

Subject: Article

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issue-copyright-statement © The Author(s) 2019