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Tamoxifen activated CreERT2 recombinase is toxic for young mice

​​​​​​​​​Mice are widely used as a model to study human diseases or to decipher gene activity or function in vivo. However, the misguided use of genetically modified mice could impair the interpretation of the results. For example, researchers at IRIG have shown that injecting tamoxifen into CreERT2 mouse resulted in unexpected toxicity and mortality.​

Published on 29 August 2023

​​Tamoxifen is frequently used in research using genetically modified mice, as it induces the transfer of the CreERT2 recombinase to the cell nucleus, which can then suppress the target genes of interest. 

Researchers at IRIG administered tamoxifen to CreERT2 young mice. Ten days later, they observed morbidity and mortality: the young mice stopped gaining weight and showed hematological defects with severe anemia and disorganization of the bone marrow vascular bed (see figure). These results show that activation of CreERT2 by tamoxifen significantly reduces cell proliferation in the bone marrow and spleen. This is due to a toxic side effect of the CreERT2 recombinase. This discovery should allow a better use of these models, improving the accuracy of the interpretation of the observed phenotype, saving time and resources. 

The results of the study carried out by the researchers show the need to include CreERT2 controls injected with tamoxifen, without targeting the gene of interest, in experimental designs.

Figure: disorganization of the bone marrow in the femur of a tamoxifen-injected CreERT2 young mouse (see arrows). Confocal microscopy: cell nuclei (blue) and blood vessels (green).

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