Berkeley Sickle mouse strain
Key takeaway
Background
The Berkeley Sickle mouse strain is highly sensitive to light, sound, and touch. Exposure to these stimuli can trigger sickling episodes in the mice that manifest as acute pain crises, similar to humans with sickle cell disease, resulting in the protocol being classified as severe. To minimise the risk of inducing pain crises and to reduce overall suffering, the facility implemented targeted refinements to husbandry and handling practices.
These refinements were designed to limit environmental triggers and improve the animals’ resilience to necessary experimental procedures. While stock animals benefited immediately from these changes, experimental animals remained vulnerable due to the unavoidable disturbances associated with moving them from the breeding area to the experimental holding area. This prompted the introduction of habituation strategies to further reduce suffering.
Refinements
- Reducing exposure to light — Main room lighting was kept at low levels, animal transfer station lighting remained off, and cardboard houses were provided. Cages were positioned on lower IVC rack levels to minimise overhead light exposure.
- Reducing exposure to sound — Animals were housed in a quiet end room on the breeding floor, limiting footfall and disturbance. The tannoy system and radio were switched off in that room, and signage was used to prevent unnecessary disturbances.
- Reducing exposure to touch — Refined handling techniques were adopted, using tunnel handling instead of cupping, with slow and gentle movements to avoid triggering pain crises.
These refinements successfully prevented stock animals from entering pain crises. However, experimental animals continued to experience pain episodes due to the increased human traffic, light, and sound when they were moved to the experimental holding areas.
- Habituation — Transferring experimental animals to the experimental holding areas at an earlier age allowed them to acclimatise to increased handling and environmental disturbances. Younger mice demonstrated greater resilience and did not enter pain crises. This enabled their use in experimental studies, reducing the total number of animals required and lowering overall suffering.
Implications
Refining husbandry, handling, and implementing habituation strategies effectively reduces pain crises and suffering in Berkeley Sickle mice. These improvements allowed the facility to downgrade the protocol severity classification from severe to moderate.