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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Project grant

The behaviour of laboratory mice as an indicator of welfare state in genetically modified mice

A rat being held by a hand with a glove

At a glance

Completed
Award date
May 2005 - September 2006
Grant amount
£135,621
Principal investigator
Professor Christine Nicol
Institute
University of Bristol

R

  • Refinement

Overview

Project background

Genetically modified (GM) mice are used extensively as human disease models, including chronic and degenerative diseases. Humane endpoints are identified to ensure that as the disease advances animals are euthanised ideally before the onset of clinical symptoms that compromise welfare. Methods for detecting humane endpoints in GM mice can be time-consuming and may increase animal stress if they require extensive handling.

Why we funded it

This Project Grant aims to refine the use of GM mice by identifying behavioural changes that can be used to indicate reduced welfare state. This will be allowed for by providing a suitably enriched environment where changes in home-cage behaviours can be observed objectively allowing early intervention and better human endpoints. 

Research methods

Not all mouse behaviours are of equal importance to the animal. Conditions, such as disease, can result in a reduction or ceasing of particular behaviours. Behaviours essential for survival, such as eating and drinking, will be performed at the same frequency even in harsh conditions. Other behaviours, such as monitoring the environment or seeking novelty are less resilient and these are often the first to be lost as an animal readjusts its priorities. By providing a suitably enriched cage which permits a wide range of high and low priority behaviours, the detection of behavioural changes indicating reduced animal welfare is possible. The future aim is for observed changes in behaviour to be identified automatically in the home-cage environment. 

Application abstract

The aim of the project is to use home-cage behaviour as an accurate indicator, and ultimately predictor, of pain and distress in laboratory rodents. The project is designed to test the hypothesis that appropriate environmental enrichment can be used, not just to refine living conditions for laboratory rodents, but also as a method for detecting subtle changes in behaviour that reflect impaired welfare. An environment more complex than the standard laboratory cage will allow the expression of species-specific behaviour demanding a range of cognitive and motor skills. It is important to detect the onset of pain or discomfort in genetically modified mice using the most sensitive techniques. Behaviour, as the integrated expression of detectable physiological change, has the potential to provide the most sensitive point of detection. The project will first seek to examine the effects of a specific enriched environment on overall welfare and on the approximately timing of onset of genetically determined deficits. The project will then assess the value of using home-cage behaviour as a sensitive indicator of welfare by examining individuals of two genetically-modified lines housed either in control or enriched environments. The interpretation of changes in home-cage behaviour will be made by reference to conventional indicators of welfare, correlation of change with observations made using standard screening protocols for humane endpoints and correlation of change with performance in screening protocols designed to detect deficits in genetically modified mice.

Publications

  1. Littin K et al. (2008). Towards humane end points: behavioural changes precede clinical signs of disease in a Huntington's disease model. PNAS 275(1645):1865-1874. doi: 10.1098/rspb.2008.0388