Mice can be a valuable model for early biomedical research, but many of the drugs that demonstrate promising results in these animals still fail in human trials. There are multiple reasons for this, but researchers are beginning to realize that environmental factors such as the microbiome may also have an effect. In most preclinical work, researchers use inbred mice that express specific genes and are raised in sterile environments.
Rosshart and colleagues addressed this situation by implanting lab-strain embryos into wild mice. The resultant “wildlings” had a systemic immune phenotype and a bacterial, viral, and fungal microbiome much closer to those of their wild counterparts and may therefore be a better predictor of human responses to some drugs than commonly used lab mice. The authors repeated two preclinical studies that had demonstrated positive results in mice but failed when they reached human testing. Interestingly, with the new models, the team saw results that resembled the drugs’ effects in people rather than the previously misleading mouse results.
The authors state that they don’t want to create the impression that laboratory mice are not useful, but that it might be possible to better mirror a clinical relevant situation with laboratory mice. They also emphasized that the “wildlings” may be better suited for certain types of research such as immunology.

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