Implementation of non-aversive mouse handling for welfare refinement and reduction of mouse numbers

Animal care staff usually lift laboratory mice by their tails when undertaking routine procedure such as health checking, cage-cleaning and performing scientific duties such as giving injections. Unfortunately this can cause stress and mice to become anxious, which can lead to them providing less reliable scientific results. Preventing stress and anxiety would therefore not only improve welfare but might also increase the quality and reliability of research findings. Ultimately, this could lead to fewer animals being needed for studies to be successful. This has obvious advantages in terms of animal welfare costs, but would also lower the financial costs of studies. It is now known that handling mice in cupped hands can reduce their anxiety, and that it is even better to use an open-ended clear plastic tube (known as non-aversive handling (NAH) tunnel). Despite this, both animal care and research staff still seem to prefer tail-lifting. This seems to be primarily due to concerns that NAH would increase the time and consequently the costs associated with performing routine husbandry procedures. Understandably, researchers also worry that changing the method by which their mice are handled may alter their behaviour, or have other hidden effects making data interpretation more difficult. However, recent research suggests, not only that these concerns are unlikely to be valid, but that mice adjust more rapidly to handling-tunnels than was previously thought. Whether researchers breed their own mice or obtain them commercially, animal supply costs are another main study running cost. According to one major breeder, stress caused by routine care procedures can significantly lower breeding performance; raising the possibility that tunnel handling could also lead to more efficient animal production, which would ultimately lower animal supply costs. The main aims of this project are therefore:

1: To address the issues preventing more widespread use of handling-tunnels; to what extent are the present barriers due to staff or animal training and how can they be broken?
2. To assess NAH as a means of improving welfare in a broader context; can the benefits be realised in several different laboratories?
3. To establish whether tunnel-handling enhances or harms the quality of scientific results and evaluate whether it has potential for lowering animal use.
4. To establish if it improves breeding success; generally enabling more efficient use of scientific resources.

We believe the best way of achieving these aims is to engage with researchers in our own research facility who have expressed concerns about implementing NAH, but also those working outside the UK where it is even less common; one in the USA and one in Italy. With guidance from the applicants they will begin using NAH and report on their experience of its implementation. By comparing their findings with mice that have undergone NAH with equivalent mice that have been tail-lifted will allow us to determine if quality and efficiency has been improved. We believe that once these researchers experience the welfare and scientific benefits of NAH that they will publish their findings and so encourage wider use of the technique.

Stress can result in anxiety, which is an unpleasant emotional state that humans working with animals wish to avoid. Anxious animals may cope poorly during scientific testing and provide inconsistent data, which is reflected in increased statistical 'noise', lowering the fidelity of results, and ultimately leading to greater numbers of animals being needed for reliable hypothesis testing. Techniques such as counterbalancing and blinding during data analyses can help to maximise precision. However, stress-related variation in data is still a major problem. For example, animals unwittingly exposed to sub-optimal housing can perform unreliably in behavioural studies. However, stress and anxiety also impact upon numerous physiological systems and generally compromise the biologic equilibrium, so can be detrimental to studies regardless of the measurement of interest. Handling laboratory mice is an unavoidable consequence of procedures and a significant cause of anxiety that has until recently has not been avoidable without using potentially even more confounding interventions (e.g. anxiolytics). However, there is now compelling evidence that 'non-aversive' handling (NAH), a relatively simple method alteration, whereby mice are lifted using a tunnel rather than by their tail can lower their anxiety; enhancing welfare, but also increasing the chances of obtaining more precise research results. The project will engage 3 local research groups (on liver disease and cancer) and 2 working internationally (cardiac disease and neuropathic pain) to test the reproducibility of NAH for both improving welfare and data precision across several scientific disciplines. These would use NAH for the first time, providing immediate uptake and knowledge transfer and an ideal opportunity to challenge common misconceptions, such as that it is too time consuming or difficult than tail-handling, and show that it can even prevent anxiety from procedures such as restraint or giving injections.

Mice are currently the most widely used laboratory species both in terms of total numbers and according to the diversity of available out-bred, inbred and genetically altered models. As such they are not only the species at most risk of poor welfare, but also the one where there is greatest potential for welfare enhancement via implementing methodological refinements. However, such refinements, other than those that are prohibitively costly or can only be applied following rigorous welfare evaluation, are generally rare. The discovery that non-aversive handling (NAH; i.e. using a tunnel rather than using traditional tail-lifting) can substantially reduce the degree of stress and anxiety associated with routine laboratory care and scientific testing procedures represents one of the most potentially effective advances seen in recent years. This is because, apart from their negative impacts on welfare, stress and anxiety are major sources of unwanted experimental noise that can lead to more to variable research findings. This variation tends to lower the consistency of results obtained in studies, and ultimately, to more mice being needed to achieve specific scientific objectives. The positive impact of NAH is therefore not limited to the benefits mice receive, but could also benefit scientists by lowering the costs associated with running studies, and consequently allow more efficient allocation of resources. Similarly, the cost of breeding mice is increased if they do not breed efficiently, and stress and anxiety from repetitive checking of health and reproductive status (such as whether copulation has occurred or if dams are pregnant and healthy) could unwittingly be contributing to poor breeding success. Avoiding this via use of NAH could therefore be both financially beneficial as well as beneficial to welfare as early as the animal supply stage.