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Updated: Aug 7, 2026
Transthoracic Echocardiography in Mice
Published on: May 28, 2010
Cre toxicity in mouse models of cardiovascular physiology and disease
Victoria S Rashbrook1, James T Brash1, Christiana Ruhrberg1
1UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Abstract:
The Cre-LoxP system provides a widely used method for studying gene requirements in the mouse as the main mammalian genetic model organism. To define the molecular and cellular mechanisms that underlie cardiovascular development, function and disease, various mouse strains have been engineered that allow Cre-LoxP-mediated gene targeting within specific cell types of the cardiovascular system. Despite the usefulness of this system, evidence is accumulating that Cre activity can have toxic effects in cells, independently of its ability to recombine pairs of engineered LoxP sites in target genes. Here, we have gathered published evidence for Cre toxicity in cells and tissues relevant to cardiovascular biology and provide an overview of mechanisms proposed to underlie Cre toxicity. Based on this knowledge, we propose that each study utilising the Cre-LoxP system to investigate gene function in the cardiovascular system should incorporate appropriate controls to account for Cre toxicity.
Insights
Cre recombinase activity can harm cells, independent of gene editing. Researchers recommend controls for Cre toxicity in cardiovascular studies using the Cre-LoxP system in mice.
Area of Science:
- Cardiovascular Biology
- Genetics
- Molecular Biology
Background:
- The Cre-LoxP system is crucial for genetic research in mice, particularly for studying cardiovascular development and disease.
- Engineered mouse models utilize Cre-LoxP for cell-specific gene targeting within the cardiovascular system.
Purpose of the Study:
- To review existing evidence of Cre recombinase toxicity in cardiovascular research.
- To outline proposed mechanisms underlying Cre toxicity.
- To emphasize the need for controls against Cre toxicity in cardiovascular studies.
Main Methods:
- Literature review of published studies on Cre toxicity.
- Analysis of mechanisms contributing to Cre-induced cellular stress.
Main Results:
- Accumulating evidence indicates Cre activity can be toxic to cells, irrespective of its DNA recombination function.
- Specific examples of Cre toxicity in cardiovascular-relevant cells and tissues are documented.
- Proposed mechanisms for Cre toxicity include off-target effects and cellular stress responses.
Conclusions:
- Cre toxicity is a significant consideration in Cre-LoxP based cardiovascular research.
- Studies using Cre-LoxP in the cardiovascular system should implement controls to mitigate or account for Cre toxicity.
- Further research into Cre toxicity mechanisms may improve the reliability of genetic studies in cardiovascular biology.
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