Reduction and refinement of mouse usage with in utero engineered mouse models

Genetically engineered mice are the current state of the art for understanding gene function, lineage tracing studies, and more.

However, these mouse models entail by-production of mice of the wrong genotype, and can require complex breeding schemes or treatment of animals with chemicals.

To circumvent these issues and reduce mouse usage, my lab has been pushing in utero injection beyond the state of the art to directly in utero engineer mouse models, without the need of dedicated genetic mouse strains or chemicals.In utero injection allows precise control over the number of manipulated mice, reducing the production of unwanted mice by 50-99%.

My lab has shown that in utero injection into the amniotic fluid of mice at embryonic day 7.5 can manipulate up to 99% of brain cells, providing a new and highly efficient method to study gene function in the nervous system.

We and others have used this approach to study neural lineages.Now, we aim to (1) refine the injections with robotics and artificial intelligence (to shorten injection times and improve reproducibility, reducing mouse usage further), and (2) adapt in utero injections to target mesoderm, and its derivatives such as heart, muscle and kidneys.

To understand mesoderm targeting and development, we will perform single cell barcode lineage tracing from our transduced mice.This project can dramatically reduce the ethical costs of animal research in multiple fields, while providing new fundamental insights.