The Principles of the 3Rs

Using ultrasound to determine mouse pregnancy

Several research groups at the LMB require early-stage mouse embryos to aid investigation into a variety of topics. The LMB’s Biological Services Group has introduced ultrasound machines and demonstrated their effectiveness at accurately determining pregnancy in as little as 5.5 days, causing the mice no distress or pain.

With an overall 35% increase in accuracy in pregnancy detection in comparison with previous methods, which relied on gentle stomach palpations, this initiative has led to a reduction in the number of mice required for studies.

Organoids: lab-grown miniaturised organs

LMB researchers can use human or mouse stem cells to grow 3D organoid structures in tissue culture to simulate complex organs of the body. Organoids can replace or significantly reduce the number of animals used in research, by facilitating studies of chosen organs in isolation from whole-body systems. While undeniably useful, organoid models are limited as they only represent one organ and cannot reflect the complexity of entire organisms.

Studying the brain with cerebral organoids

Cerebral organoids have proved valuable for studying the brain, including neurodevelopmental disorders like autism and schizophrenia. LMB researchers have also developed brain organoids capable of producing cerebrospinal fluid (CSF), which has allowed them to explore how certain drugs access the brain and how it is infected by viruses like SARS-CoV‑2.

This work has been recognised with a 3Rs Prize from the National Centre for the Replacement, Refinement and Reduction of Animals in Research.

Stem cell culture system replicates mouse gastrulation

Many of the cellular processes that occur during early embryo development are unknown. In part, this is because the developmental stage in which stem cells differentiate, known as gastrulation, is very difficult to study.

To overcome this, LMB researchers have developed an in vitro 3D model of self-renewing cells which recapitulates gastrulation. This new model makes it easier to visualise development and has allowed researchers to determine molecular triggers for key stages of differentiation.

Championing non-aversive mouse handling

Mice are handled frequently, both in day-to-day care and in the course of scientific procedures. For many years, the accepted way to pick up mice was by their tails, but research has shown that this can cause mice to experience high anxiety levels. LMB animal technicians now champion non-aversive mouse handling instead, which uses a cupped hand or a cardboard tunnel to pick up mice.

Using these new handling techniques has shown beneficial effects in the mice, such as reduced aggression and less anxiety immediately after minor procedures.