A bestiary of genetic mouse lines and related tools for inducible and reversible intersectional misexpression

Thanks to the astonishing advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. Among functional experiments, misexpression approaches are often modular, such that distinct combinations of driver and effector lines can be used to achieve different effects. However, existing combinations have pitfalls that hinder sophisticated applications like tissue-specific reversible gain-of-function. Here, we put forward an approach that can leverage existing driver modules to achieve inducible and reversible transgene misexpression with high spatiotemporal resolution, by using an effector allele that requires the intersection of two drivers, Cre and (r)tTA. We present the mouse lines generated for such an approach, as well as proof-of-principle experiments using different organs. We also show that the approach can be extended to other animal models, using chicken embryos. These new tools will facilitate unraveling biological questions that were previously impeded by technical limitations, in multiple fields and organisms.