The Cre-lox system is a powerful genetic tool used to mediate site specific recombination events in genomic DNA, enabling the development of conditional genetically modified mouse models. Compared to constitutively expressed gene mutations — such as systemic knockout (KO) or knock-in (KI) mice — Cre-lox conditional KO (cKO) or cKI mice can avoid the problem of embryonic lethality and achieve gene expression in specific tissues or at specific developmental stages, making them important tools for precise investigation of target gene functions.

Although Cre-lox recombination has provided an effective tool for studying conditional target gene functionality in mice, researchers first must identify the ideal Cre line(s) to use for their specific research study and genes of interest. Cyagen offers a variety of Cre mice (e.g. regular, inducible, fluorescent reporter, etc.) that can serve a range of research applications, including cardiology, ophthalmology, neurology, and more.

Cre Mouse Lines For Cre-lox Recombination-Mediated Conditional Model Development

Cyagen's drug screening and evaluation mouse model platform offers a wide range of Cre mouse lines, including regular Cre mice, inducible Cre mice, fluorescent reporter mice, etc., which may be used to develop a variety of cKO and cKI mouse models for your research study. By clicking on the corresponding product names, you can view the details of each mouse model along with its validation data. If you require Cre mouse lines with expression in other tissues or organs, feel free to contact us for further assistance.

Cre-lox Model Development Strategies

The Cre-Lox system goes by a few different names (a.k.a. Cre-LoxP site-specific recombination system, Cre-lox recombination, etc.), as lox/loxP are used interchangeably, with ‘loxP’ designation containing the extra ‘P’ due to the Cre-lox system’s adaptation from P1 bacteriophage. Additionally, one should note that the term ‘floxed’ indicates a model that contains the lox/loxP sites flanking a gene (a.k.a.“floxed gene”model). The combination of genetic floxing and Cre-lox breeding enables the generation of tissue-specific or inducible knockouts with a high level of control over the spatial and temporal expression of genes.

Figure 1. Mechanism of Cre-LoxP System: (A) An overview of Cre-LoxP system. 38 kDa Cre recombinase recognizes the loxP sites of specific 34 bp DNA sequences, excising the sequence and inactivating Gene Y. (B) General breeding strategy for conditional mutation using loxP and Cre driving mouse line. Tissue-specific Cre-driver crossing with Floxed alleles of gene Y leads to inactivation of Gene Y in tissues associated with Promoter X.

As outlined in Figure 1, the basic Cre-loxP recombination event is most often used for controlled excision of genetic sequences. This has been adapted to create Cre-dependent sequence knockout (KO) – depicted in figure 1 - and Cre-dependent gene expression models – such as the transgene switch strategies described below:

• Standard Use - Generate tissue-specific or inducible knockouts(e.g. Cre-dependent sequence KO), such as in the KO-first conditional allele strategy
• ransgene Switch – (Cre-dependent gene expression)
  1. Transgene Activation: A loxP-flanked “stop” sequence between the promoter and the coding sequence blocks expression (until bred with a Cre strain)
  2. Inducible Knockout(KO): A loxP-flanked transgene sequence may be removed upon breeding with a Cre strain.
• Reporter Strains - Visually confirm locations of Cre recombinase activity with loxP-flanked fluorescent protein sequences