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Confounding factors from inducible systems for spatiotemporal gene expression regulation
Rob C I Wüst1,2, Riekelt H Houtkooper1, Johan Auwerx3
1Laboratory Genetic Metabolic Diseases, Amsterdam Cardiovascular Sciences and Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
The Journal of Cell Biology
|May 20, 2020
Summary
Common gene manipulation systems like Cre/loxP and Tet-On/Tet-Off can cause unintended physiological disruptions. These systems may negatively impact endocrinology, gut microbiome, and metabolic functions, affecting research outcomes.
Area of Science:
- Molecular Biology
- Genetics
- Physiology
Background:
- Targeted gene manipulation is crucial for studying gene function and phenotypic traits.
- Existing systems like Cre/loxP and Tet-On/Tet-Off are widely used for spatiotemporal gene control.
- However, these systems can exhibit off-target effects impacting overall organismal health.
Purpose of the Study:
- To highlight the adverse physiological effects of commonly used gene manipulation systems.
- To inform researchers about potential confounding factors in gene function studies.
- To emphasize the need for careful consideration of system-specific impacts.
Main Methods:
- Review and analysis of literature on Cre/loxP and Tet-On/Tet-Off systems.
- Identification and categorization of reported off-target physiological effects.
- Synthesis of findings related to endocrine, microbiome, mitochondrial, and metabolic functions.
Main Results:
- Cre/loxP and Tet-On/Tet-Off systems can induce significant off-target effects.
- Observed adverse effects include disruptions in whole-body endocrinology.
- Disturbances in gut microbiome, mitochondrial, and metabolic functions were also noted.
Conclusions:
- The use of Cre/loxP and Tet-On/Tet-Off systems may introduce confounding variables in phenotypic studies.
- Researchers must be aware of and account for potential physiological disturbances caused by these gene manipulation tools.
- Further development of gene manipulation systems with minimized off-target effects is warranted.
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