Mouse models of rheumatoid arthritis

Key takeaway

The severity of painful disease models can be reduced by tailoring welfare assessment, refining humane endpoints based on specific indicators, and refining husbandry. It is important to regularly review and refine already established welfare assessment protocols.

Background

A pharmaceutical company introduced the G6PI, CIA and CAIA mouse models of rheumatoid arthritis, which have the potential to cause severe suffering. This prompted a re-evaluation of the company’s welfare scoring sheets and husbandry refinement protocols, with the aim of reducing suffering. The scientists and animal technologists worked together to tailor and refine monitoring systems, husbandry and procedures.

Mice used in G6PI and CAIA studies were very carefully monitored by scientists and animal technologists, to identify indicators of adverse effects and collate data on weight loss and disease scores. The observations were specific to each model, although standardised terminology was created to describe indicators. As a result, the following refinements were adopted:

A white mouse.

Refinements

  • Reducing the humane endpoint for weight loss from 25% to 20%, and adding another endpoint of a 15% weight loss that persisted for 5 days.
  • Using tailored indicators (such as soft stools for CAIA) enable study length to be reduced; e.g. the CIA studies were reduced from 30 days to 20.
  • Ensuring that disease scores include a range of indicators, as opposed to paw volume only, capturing severity more effectively and enabling endpoints to be further refined.
  • Providing additional refuges for DBA/1 male mice, eliminating aggression.
  • Providing non-tangling nesting material.
  • Ensuring easy access to water and food - when mobility is restricted, provide longer sipper nozzles and give food in dishes on the cage floor.
  • Using the Mouse Grimace Scale to help assess acute pain.

Implications

Regularly refining welfare assessment and defining early humane endpoints reduces severe suffering.