Mouse model of amyotrophic lateral sclerosis (ALS)

Key takeaway

Refined care and early screening protocols can significantly reduce suffering while still allowing for effective testing of potential therapies.

Background

The SOD1G93A mouse is a commonly used model of amyotrophic lateral sclerosis (ALS), a form of motor neuron disease which is rapidly progressive and fatal in humans. Current treatments only have a limited impact, so the SOD1G93A mouse is used to test potential therapies. Testing treatments that are intended to slow disease progression can require animals to experience clinical signs that can cause severe suffering. The life experiences of SOD1G93A mice were reviewed and refined, and a new Standard Operating Procedure was set out for caring for the animals. All investigators and animal technologists have a copy of the SOP, which has helped to avoid and reduce severe suffering.

Mouse model

Refinements

  • Early screening of motor function and muscle characteristics, to select which drugs to take forward without mice suffering extreme motor deficits.
  • Checking righting reflex twice daily from 100 days (or earlier if motor problems are apparent).
  • Using non-particulate litter and nesting material, as animals may have difficulty grooming.
  • Providing long sipper tubes and mash in a dish on the cage floor, to cater for disabled animals.
  • Treating any dehydration with an intraperitoneal injection of sterile saline, followed by close monitoring.
  • Husbandry refinements, including carrying nesting material (not litter) over from soiled to clean cage to reduce aggression, changing gloves and cleaning work surfaces between handling male and female mice. If fun tunnels are provided, remove them at 100 days to prevent disabled mice from becoming trapped.

Implications

Small refinements, such as early screening and daily monitoring, as well as husbandry and care refinements contributed to a reduction in severity levels of SOD1G93A mice.