To develop an automated, minimally-invasive or non-surgical system to assess activity, behaviour and interaction of at least two mice in the cages and setting the animals were reared in
Many common nervous system disorders, often the subject of intense research using laboratory animals, are associated with behavioural, locomotor and social deficits in humans. Several of these express multiple phenotypes that are currently assessed using batteries of mouse tests. For example, Huntington’s disease models express locomotor and learning deficits whereas mouse mutants in genes associated with schizophrenia often exhibit hyperactivity with cognitive disturbances. In order to measure these characteristics systematically and assess the validity of animal models a number of developments have led to a reassessment of how neurological and behavioural phenotyping are carried out. These include:
- Specialist cages for tracking activity.
- Phenotyping equipment allowing one to measure a range of behavioural and physical attributes e.g. social interactions, dominance, anxiety.
- Advanced software systems and algorithms for data interpretation.
Much of the sophisticated equipment and software which is available requires animals (mostly mice) to be placed in either a novel environment or single housing which may both compromise and confound model validation in addition to being detrimental to animal welfare.
Many current tests involve removing animals from their usual environment and placing them in a piece of equipment to monitor their activity e.g. the rotarod to measure locomotion. Recently, much publicity has been given to available ‘home cage’ systems. However, many of those available on the market are not the same as the caging animals are reared in. Mice have to be removed from their true home cage and are often placed in unfamiliar cages in different rooms, with different enrichment regimes and handlers.
Almost none of the equipment available on the market allows the simultaneous tracking of multiple animals and requires mice to be singly housed for the period of the test. Social isolation (singly housing) has been reported to affect mouse behaviours. Moreover, it is difficult, impractical and disruptive to rehouse male mice into groups after an experiment.
The development of an automated, non-surgical system will impact on refinement and reduction of studies using mouse models of nervous system disorders. These are disease models where pain, suffering and lasting harm can be difficult to assess and where earlier humane endpoints and interventions are needed. Additionally, animals would not need to be moved to unfamiliar cages or be singly housed for testing. Fewer animals would be needed because less variable data would be obtained from individuals.
The caging system used by MRC Harwell, the sponsor of this Challenge, is the most common in the UK and represents large potential for uptake of the solution. More broadly, the technology could impact in other fields e.g. metabolism, where mechanisms leading to weight changes (altered activity or food intake) could be investigated.
Phase 1 winners
Project teams led by:
- Professor Douglas Armstrong, Actual Analytics, £100,000.
- Dr Valter Tucci, Istituto Italiano di Tecnologia, £99,150.
- Professor York Winter, PhenoSys GmbH, £100,000.
Phase 2 winner
Project team led by:
- Professor Douglas Armstrong, Actual Analytics, £500,000.