Before describing how we can keep mice in more comfortable housing, it is worth briefly revisiting the reasons why this should be attempted. Each year, many millions of mice are used throughout the world in research institutes. As part of this process, it historically has been the norm to breed and house mice under highly standardised conditions, aiming to reduce variability in responses and the data from subsequent research. This has meant that laboratory housing for mice is typically small, barren and monotonous. For some time, it has been questioned whether such housing systems compromise the welfare of the inhabitants. There is now convincing evidence that standard laboratory housing does indeed result in behavioural and physiological responses indicative of animal welfare compromises. Perhaps of greater importance is recent evidence that housing animals under such conditions affects the animals so fundamentally (Prior and Sachser, 1995; Prusky et al., 2000; Würbel, 2001) that concerns are being expressed about the validity of the data and its applicability to other circumstances. This calls into question the very reason for the animals being housed in these conditions in the first place.

There are compelling welfare and scientific reasons why we should house laboratory mice under conditions more suited to their own species-specific needs. These two factors are addressed separately below, with an emphasis on how they are inter-related.
 

Laboratory housing for mice has evolved from designs that were initially primarily concerned with economics, human convenience and extreme standardisation of the environment. This means that in current systems, the behavioural requirements of the animal are largely not catered for, other than the basics of feeding and drinking (Figures 1a & b). When given the opportunity, laboratory mice show a diverse behavioural repertoire: they seek a wide variety of foods, are physically very active, form complex social organisations, build tunnels and construct nests (Jennings et al., 1998). All these behaviours are thwarted by standard husbandry and housing. Housing systems should allow animals to perform most natural behaviours (e.g., "The Five Freedoms"; Farm Animal Welfare Council, 1997) to avoid compromises of welfare. In addition, if animals are prevented from performing behaviours for which they have a strong motivation, this can lead to suffering and adverse mental states such as frustration, depression and anxiety (Dawkins 1990; Duncan, 1992; Sherwin and Nicol, 1998). Certainly, conventional standard laboratory housing prevents many natural and highly motivated behaviours [e.g., nesting, tunnelling, extensive locomotion]. As a result, mice in laboratory conditions frequently exhibit so-called abnormal behaviours, for example stereotypies (Würbel et al., 1996; Nevison et al., 1999a), indicating that mice experience chronic frustration when placed in conventional, non-enriched cages (Sherwin, 2000). Furthermore, the sensory capabilities of mice have rarely been considered in laboratory housing and husbandry design. Mice have sensory modalities that are sometimes very disparate to humans [discussed below]. Our historical ignorance of these sensory capabilities means that standard housing generally does not take into account the perceptions of mice. This is potentially the equivalent to rearing animals under conditions of sensory deprivation or interference (e.g., olfactory "white noise") with all the concomitant compromises in welfare (Cummins et al., 1977; van Praag et al., 2000).

Figures 1a & b. A human perspective and a mouse perspective of a standard laboratory cage. The inside view of a standard cage shows this design caters little for the species-specific characteristics other than feeding and drinking.

  

Animals reared in barren conditions are generally more sensitive to environmental perturbations or differences between laboratories. Therefore, when mice reared in conventional, barren cages are moved to a new laboratory, their behaviour might not be representative of "normal" responses. Moreover, there is growing evidence that the minimalistic environments of laboratory mice impose constraints on behaviour and brain development such that many studies using these animals may have little external validity, particularly in neuroscience studies. Studies may achieve good internal validity (i.e., reduced variation between animals in the same experiment in the same laboratory), but there might be increased variation between animals undergoing the same experiment in different laboratories (Crabbe et al., 1999). This diminished external validity calls into question the reason for keeping mice in conventional, barren cage. It can arise in three ways (Würbel, 2001):

1. Neurophysiological changes. It is well established that in rats, barren environments, compared to enriched ones result in decreased numbers of brain neurones, synapses and dendritic branches, especially in the cortex and hippocampus. This results in impaired learning and memory (Rosenzweig and Bennett, 1996; van Praag et al., 2000). It has been argued that such effects suggest animals reared under standard laboratory conditions experience something akin to sensory deprivation (Cummins 1977; van Praag et al., 2000).
       
2. Chronic thwarting of behavioural response rules. Animals respond largely according to evolved rules that depend on specific environmental features. If these features are absent, the animal might display inappropriate behaviour. For example, gerbils will develop stereotyped digging if they do not have a suitable shelter. This stereotyped behaviour is prevented if they are presented with a shelter, but only if the shelter has a tunnel-shaped entrance (Wiedenmayer, 1997). Thus, barren cages can limit the opportunity for animals to develop appropriate behaviour with consequences for later studies in which it is assumed the animal is behaving "normally". In addition, chronic thwarting of behavioural responses can lead to stereotypies, associated with functional changes in the dorsal basal ganglia and a general tendency to perseverity [inability to be flexible in behaviour] (Albin et al., 1989; Ridley, 1994; Hauber, 1998). This could easily lead to scientists using an animal model that is fundamentally flawed.
      
3. Mismatch between postnatal and adult environment. The barren, monotonous environment in which mice are reared very often conflicts with the more variable life of mice undergoing research later in adult life. This can have a profound influence on the validity of the research. Laboratory-reared mouse pups are less stimulated than their wild counterparts as the laboratory-mother leaves the nest less frequently and for only short periods because food and water are provided nearby. However, if pups are handled for just a few minutes each day, the mother increases visits to the nests and grooms the pups to a degree that is thought to more accurately represent what is adaptive in the wild. As a consequence, pups who have been handled and thus better attended to by the mother [which might be encouraged by cage design and enrichment rather than handling] show reduced behavioural and endocrine responses to stress (Würbel, 2001). This could manifest as a reduced sensitivity to procedures causing pain, distress or suffering. In addition, barren environments at an early age can lead to improper development of the senses, e.g., vision (Prusky et al., 2000) with obvious consequences for studies requiring "normality" of these senses. The mismatch between postnatal and adult environment caused by standard laboratory housing is likely to have considerable, multifarious implications for research conducted on animals housed in these systems.

There is often great concern about the harm, distress and suffering caused by particular research procedures upon mice, however, it must be remembered that almost ALL mice used in research - including breeders, stock, "spare" mice, and mice used in non-invasive studies - will be placed under standard housing conditions. This may be for considerable periods of time before the study itself, and might persist afterwards. Therefore, the suffering caused by inappropriate housing and the lack of enrichment may well be of greater duration than the suffering caused by research-related activities. Arguably, the intensity of housing-related suffering might also be of greater intensity than that caused by the study. What is of great importance, however, is that the suffering caused by inappropriate housing and the lack of suitable environmental enrichment, will be experienced by a great proportion of all laboratory mice.
 

To make life more comfortable for laboratory mice, we need to understand their species-specific characteristics. In particular, we need to understand their sensory perceptions and motivations. Therefore, the following sections summarise what we know about how mice perceive the world and how they behave. This is discussed in the context of how we might provide a better environment to address these species-specific requirements. It should be remembered, there is now available a bewildering diversity of strains of laboratory mice. Many of these have specific requirements [e.g., nude and ob-ob mice may have problems with thermoregulation]. Similarly, wild mice are different in many ways from their laboratory cousins (Jennings et al., 1998). It is impossible to consider all these requirements in this volume, so caretakers and investigators should make themselves aware of any particular idiosyncrasies of the strain they are working with and take appropriate action.
  

Laboratory mice have [at least] the same five senses as humans, but these are used in different ways, which can make them difficult for us to imagine. Because we are unable to perceive the world in the same way as a mouse, and we have been historically ignorant of their senses, several aspects of the environment we provide have a direct impact on their perceptual capabilities and, ultimately, welfare status.

Olfaction

We humans use olfaction consciously very little, so this aspect of the mouse's perceptive world is almost totally hidden from us. But, olfaction is perhaps the most important sense used by mice, particularly in their highly complex social organisation. It is therefore important as a welfare concern, to understand the role of olfaction in mouse behaviour.

Mice create patterns of urine deposition for territorial marking and individual as well as group recognition (Hurst et al., 1993, 1998; Humphries et al., 1999; Nevison et al., 2000). Odours from adult males or from pregnant or lactating females can speed up or retard sexual maturation in juvenile females, and synchronise reproductive cycles in mature females. Odours of unfamiliar male mice may terminate pregnancies (Jennings et al., 1998). It has been shown that laboratory mice rendered surgically anosmic and then housed in large semi-natural enclosures interact with each other very differently from intact mice. Anosmic mice show very little aggression, roam freely about the enclosure rather than confining themselves to particular areas, and generally ignore each other. When they do encounter another individual, they appear startled and move away from each other (Liebenauer and Slotnick, 1996).

The use of olfaction by mice in mediating social encounters means that cage cleaning can be problematic (Gray and Hurst, 1995). There are two conflicting pressures: the need to clean cages for hygiene and health, and the need not to disturb scent-marking patterns too frequently. It has been shown that standard methods of cage cleaning, in which only the substrate and parts of the cage are washed clean of scent marks can be detrimental to male mice by promoting aggression. It has been recommended that if aggression is likely to be a problem, mice should be transferred into completely clean cages with fresh bedding (Jennings et al., 1998) or nesting material is moved with the mice (van Loo et al., 1988; Figure 2). It has also been suggested that strange odours [e.g., those associated with humans such as perfumes and deodorants] can produce stress responses in laboratory mice (Dhanjal, 1991). This should be taken into account when cleaning cages and handling the animals.

Figure 2. Nesting material is easily provided for mice in standard laboratory cages. This is an inexpensive enrichment yet it probably represents the most cost-effective enrichment that can be given to mice in terms of its great impact on improving welfare and reducing aggression after cage cleaning.

Clearly, olfaction plays a critical role in the social behaviour of mice. Therefore, it is of great concern that inbreeding of laboratory mice can result in male mice becoming unable to discriminate between their own scent marks and those of other males (Nevison et al., 2000). This obviously could have considerable influence on behaviours such as agonistic and aggressive encounters and could easily affect responses in experiments. In addition, the lack of olfactory stimulation at an early age might influence performance in behavioural studies dependent on this sensory modality [e.g., discrimination studies] (Mihalick et al., 2000; Forestell, et al., 2001), learning and memory (Schellinck et al., 2001) and predator-related studies (Dellomo and Alleva, 1994).

Rats are natural predators of mice, and mice will show fear responses when they encounter anaesthetised rats (Blanchard et al., 1998). If housed in the same room, mice might become aware of rats by olfaction, even if they can not see them. Therefore, mice and rats should always be kept in separate rooms (Jennings et al., 1998). Similarly, it may be a wise precaution to change clothing and wash hands after handling predator species, such as rats and cats, or their bedding to avoid causing fear reactions in mice.

Hearing

Mice can hear over a broad spectrum of frequencies. They can detect frequencies from 80 Hz up to 100 kHz, but are most sensitive in the 15 kHz to 20 kHz range and around 50 kHz (Jennings et al., 1998). This means they can hear well above the frequency of human hearing sensitivity.

Both audible and ultrasonic calls are used by mice in a variety of situations. Audible vocalisations can often be heard during agonistic encounters, whereas ultrasound is known to be used in sexual communication and also by pups when they have fallen out of the nest. It has even been reported that rats and shrews use ultrasound for echolocation (Kaltwasser and Schnitzler, 1981; Forsman and Malmquist, 1988).

Like many other laboratory mammals, mice are more sensitive than humans to sudden bursts of noises. They probably find sound pressure levels aversive when these are at an intensity 20 dB less than humans find aversive. Juvenile mice can become sensitised to loud sounds, including ultrasound. In some strains, this can increase the incidence of audiogenic convulsions or seizures (Gamble, 1982), decreased activity, reduced fertility and changes in blood glucose and corticosteroid levels [i.e., indicators of chronic stress].

Several items of common laboratory equipment such as pressure hoses, running taps, computer monitors or oscilloscopes can emit ultrasound at very high sound pressures (Sales et al., 1988, 1999). This is silent to humans, but could have considerable effects on the welfare of mice. Laboratory-generated ultrasound may interfere with communication between mice, causing distress or perhaps even sensory damage. This is likely to remain undetected by the staff. Furthermore, when many mice are housed in a large laboratory, or in high stocking densities within cages, the number of ultrasonic calls being given at any one time could be very great. This could result in the mice perceiving the environment to be very noisy and potentially stressful - rather like humans being in a crowded room with everyone shouting to each other - but human animal attendants would be totally unaware of this noise. Commercial "bat detectors" register ultrasonic frequencies and could be used to detect whether equipment is generating ultrasound, or when mice are vocalising to each other or in response to distressful procedures such as blood collection and injection. In this way, monitoring of ultrasonic vocalisations could be used to help in overall assessment of mouse welfare.

Items that routinely make loud noises [e.g., alarms, telephones, door-bells] should be designed to operate at frequencies less audible to the rodent ear [e.g., below 500 Hz]. It has often been suggested that a radio playing softly in the background can be a suitable enrichment and that this makes mice more tractable and less responsive to sudden noises. I have not seen any scientific evidence to support this, and it should be remembered that at least some of the sound produced by radios will be below the frequencies to which mice are sensitive. However, the radio may provide more comfortable quarters for the human caretakers, which in turn could have beneficial consequences for the animals.

Vision

Although mice have good vision, this sense is perhaps less important than others. In the wild, most mice are nocturnal and usually avoid brightly lit areas. Therefore, the light intensities in which we keep laboratory mice are relatively high compared to the environment in which they have evolved. These higher light intensities can lead to eye abnormalities, including the induction or exacerbation of retinal atrophy (Jennings et al., 1998). This, of course, can result in gross disturbances to visual perception, a particular problem for albino strains lacking protective visual pigment, and for individuals in top-row cages that are not shaded by a row of cages above them. To protect mice from intense illumination, cages - especially transparent cages - should be provisioned with nesting material, and a light baffle [sheet of wood or plastic] placed over the top row.

Prusky et al. (2000) demonstrated that enriching the environment of mice early in life led to significantly improved vision. Pups reared from birth in large, clear cages with enrichment objects had 18% better acuity than pups reared under standard laboratory conditions. This shows clearly that the mouse's visual system can be significantly influenced by the nature of early visual input.

The visual apparatus of mice is basically similar to humans, with the exception of its sensitivity to ultra-violet light. The ventral area of the mouse retina has a denser accumulation of ultra-violet sensitive cones (Calderbone and Jacobs, 1995; Szel et al., 1996; Yokohyama and Shi, 2000; Neitz and Neitz, 2001). The biological significance of this structure is not yet known. Humans with normal vision are insensitive to ultra-violet light [the cornea blocks it] and as a result of this, we have designed artificial lights, including those used in laboratories, to emit very little ultra-violet radiation. Although the consequences of housing mice under lights with little ultra-violet output have not been experimentally determined, other species with ultra-violet sensitivity prefer areas supplemented with these wavelengths (Moinard and Sherwin, 1999) and housing them without ultra-violet causes physiological and behavioural disturbances indicative of welfare compromise (Maddocks et al., 2001). Placing an animal with ultra-violet sensitivity into an environment without these wavelengths is likely to distort their perception of all colours, not simply seeing the world minus one colour. These colour shifts could give the mouse a distorted visual perception of his/her world, rather like humans seeing a psychedelic picture. Although the welfare implications of ultra-violet sensitivity are undetermined, this should be considered and further research in the area encouraged.

The above studies all indicate that the visual environment of standard laboratory housing is often inappropriate for mice and can lead to impaired vision. Many behavioural tests in research institutes are totally dependent on vision, yet we rarely account for the visual experience of the animal and how "normal" his or her perceptive capabilities might be. Also related to vision and behaviour, mice are generally nocturnal, yet routine husbandry - including handling and inspection of the animals - and many tests are performed under bright lights or during the light phase when the animal would normally be asleep. This leads one to question, perhaps rather anthropomorphically, the validity of data from such tests: would we trust data from behavioural and physiological tests when these had been gathered from humans chronically sleep-deprived by being repeatedly woken up in the middle of the night!

Whenever possible, the lights should be put onto a reverse light:dark cycle. With the aid of a dim red light, the mice can be inspected and handled during the dark phase when they would normally be active. In addition, lights can be programmed to gradually increase or decrease in intensity to provide an artificial dawn or dusk, a circumstance that is thought to give animals the opportunity to prepare for periods of inactivity or activity [e.g., by eating a little extra food, or building nests].

There is some evidence that mice prefer opaque cages to transparent cages (Baumans et al., 1987). This might be related to light intensity, or seeing neighbouring mice in close proximity but being unable to assess their status by olfaction. Whichever, providing nesting material will benefit the animals if they have to be kept in transparent cages.

Touch

Touch is an important sense for mice. In times of stress, mice retain contact with surfaces (Berry, 1981). Loss of tactile contact with conspecifics seems to be the most important factor in determining the isolation-induced increase in aggressiveness in male mice (Brain and Benton, 1983). When moving about, mice like to remain in contact with a wall and generally show avoidance of open spaces, i.e., thigmotaxis. This preference can be catered for in cages by providing dividers in either the vertical or horizontal planes. They add complexity to the cage and might also increase the size of the cage as perceived by the mice. It has been reported that vertical cage dividers can reduce fearful or anxious behaviour in a novel environment (Boyd and Love, 1995). Some commercial pet companies produce “mazes” for rodents that could be practical enrichment for laboratory mice. The “mazes” are essentially small cages with many vertical dividers and a transparent, removable lid making it easy to locate and catch the mouse.

The facial-vibrissae, or whiskers, are acutely sensitive touch organs used to investigate novel objects, or during thigmotaxis when moving about the environment. Laboratory mice sometimes engage in a behaviour called whisker-trimming, or barbering, in which one mouse trims the vibrissae of another, sometimes totally. The significance of this behaviour is unclear. It has been hypothesized to be a dominance behaviour (but see van de Weerd 1992; Garner et al., 2001), however, rather bizarrely, it has been shown that if a pair of mice are separated by wire mesh, whisker-trimming continues (Vandenbroek et al., 1993). This indicates some co-operation by the mouse who is being whisker-trimmed, and it was argued that whisker-trimming might lead to the release of endorphins [i.e., mice co-operate in this behaviour as a form of “coping response” to a stressful situation]. Whisker-trimming does not appear to have been reported in wild mice, suggesting that laboratory conditions might predispose this “abnormal behaviour”. Whatever the underlying cause or function, if laboratory conditions result in whisker-trimming, this indicates the standard environment potentiates a behaviour that causes at least some mice to lose one aspect of their sense of touch. Therefore, any enrichment that prevents this behaviour is probably improving welfare.

Many mouse cages in research institutes have wire mesh or grid floors. These prevent us from providing mice with floor substrate. This in turn thwarts several behaviours that the mice are motivated to perform and can also result in health problems such as pressure sores (Hubrecht, 1995) and urological problems (Everitt et al., 1988). These problems are addressed by the Guide for the Care and Use of Laboratory Animals, stipulating that “Solid-bottom caging, with bedding, is therefore recommended for rodents” (National Research Council, 1996, p. 24). Blom (1993) showed that mice prefer a solid resting site and will generally spend more time on a solid surface rather than a grid floor (Blom et al., 1996). Although it might not be possible to change the entire floor structure, at least a section of the cage floor should be covered, or a receptacle of substrate provided for resting. The mice will avoid soiling this substrate [see “Eliminative behaviour”] meaning it stays relatively clean and does not have to be changed frequently.

Taste

Mice are used as a model species for humans in studies relating to taste. Presumably then, mice have taste apparatus and taste sensations similar to those of humans. Wild mice will eat a wide range of foods such as seeds, fresh vegetables, fruit and bread (Jennings et al. 1998), and where this does not interfere with the objectives of the research, such food should be offered as an alternative to or a supplement of the standard laboratory rodent pellet. If a standard diet is given, expanded forms appear to be more palatable than pelleted, presumably due to the difference in texture and taste (Jennings et al., 1998).

Differences in taste preferences have been reported for different strains of laboratory mice (Frank and Blizard, 1999). In addition, behavioural studies have shown that mouse pups readily develop preferences for the same food that their mother eats, and that the strength of this preference is dependent upon the taste properties of the food (Valsechhi et al., 1993).

Food can affect odour cues of mice, and a group of animals kept on the same diet may have more difficulities discriminating between individual group members than animals kept on a variety of different diets (Brown et al., 1996). This suggests that providing varied diets might increase the ability of cage-mates to discriminate amongst themselves and therefore possibly reduce agonistic or aggressive encounters. Scalera (1992) observed in rats that taste preferences, water consumption and food consumption can all be significantly different depending on whether the animals are housed singly, in pairs or groups, and warned that for experiments in which appetite and taste are dependent variables, the animals should be housed under similar social and environmental conditions.

A commercial product [rather comically designed as a huge mouse] has recently become available for pet rodents (Figure 3). Favoured food is placed in the gadget which has several holes. The aim is to encourage the mouse to push the puzzle about the cage to get the food to eventually drop through one of the holes. Although the effectiveness of this gadget as an enrichment tool for laboratory mice has not been tested, the principles of increasing food diversity and allowing the animal to work for food suggest this would improve welfare.

Figure 3. A standard mouse cage enriched with a pet rodent "drop feeder" to make the mice work for an alternative food, shredded paper for nesting material, a running wheel and a chewing block.

 

The behaviour of laboratory mice can be complex. Detailed ethological analyses of caged animals reveal more than 40 different, commonly exhibited activities and postures. (Jennings et al. 1998). However, there are several behaviours that laboratory mice readily perform when given the opportunity, but which are normally thwarted by the small size or barrenness of standard cages. These are outlined below, along with suggestions of how enrichment might allow mice the opportunity to perform these behaviours.

Nest-building

Mice will build nests with much apparent enthusiasm (Figure 2). This not only helps them to protect their young, but in non-breeding animals can also help to regulate temperature and light levels and to hide and retreat from cage-mates or other threatening stimuli. There is considerable evidence that mice are strongly motivated to build nests (Blom 1993; Sherwin 1996; 1997; van de Weerd et al., 1998), indicating that this activity fulfils one of their most fundamental behavioural needs.

Several products are commercially available, but hay, straw, shredded paper, wood chips and paper tissues are all useful. Paper towels can be left on the cage lid for the mice to energetically drag through the bars and chew into pieces to build a nest. If several materials are available, mice will generally build a composite nest (Figure 4). Although providing nesting material is easily and inexpensively achieved, it is one of the best and most versatile enrichments for mice kept in research institutions. Suitable nesting supply should be provided for all animals, although for cages with new-born young, materials that might entrap legs should be avoided [e.g., cotton wool, wood wool, shredded paper] and materials that absorb moisture as these can stick to wet pups and cause dehydration.

Figure 4. A cup-shaped nest. In this study, the mice removed both types of bedding material offered to them in the containers, and built a composite nest.

Increased Activity

Mice are extremely active animals, yet the physical dimensions of a standard sized cage allow mice to move only a few body lengths in any one direction. This spatial restriction, in conjunction with a plentiful supply of food nearby, means that mice can quickly become overweight with a subsequent reduction in life-span. They demonstrate a strong motivation to gain access to additional space to that provided by a standard laboratory cage, even when this provides no further resources or enrichment (Sherwin and Nicol, 1997); this could be interpreted as the mice having a strong urge to escape standard laboratory conditions!

One method of providing an opportunity for increased activity is a running wheel (Figure 5). There is much evidence to suggest that providing a running wheel is of great benefit. Mice will work hard to gain access to a wheel, they prefer a wheel to an extended surrogate tunnel system, and there are many physiological and behavioural advantages related to welfare. Mice sometimes appear to play in running wheels. For example, they will grip the rungs of the wheel until they are carried around and around by the wheel's momentum. They will turn motorised wheels on and off. It has even been reported that mice prefer wheels that have been made into irregular shapes, or include hurdles to jump over (Sherwin 1998 a,b).

Figure 5. Running wheels are suitable to promote exercise in captive mice.

Other methods can be utilised to encourage increased activity, even within the confines of a relatively small cage. Simple activity discs can be made relatively easily and cheaply (Figure 6; Animal Welfare Institute, 1979). Commercial pet companies manufacture "activity dishes" which resemble a miniature satellite dish set at an angle to rotate about a central axis (Figure 9). Climbing frames, ropes, pieces of string or chains all allow mice to climb. In addition, the bars of the cage-lid are used prodigiously; if taller cages are used, enrichments allowing access to the lid should be provided. For this reason, amongst others, cages with solid tops are not recommended.

Figure 6. Activity discs can be made relatively easily and cheaply (Photo by Ernest P. Walker, 1979).

Tunnel-building

Many wild rodents build complex tunnel systems (Ellison, 1993; Schmid-Holmes, 2001). These are used to escape predators (Blanchard et al., 1995) and presumably for other comfort factors including thigmotaxis. Laboratory mice who have never had the opportunity to dig tunnels will build these within a few hours if a suitable substrate is provided (Sherwin, personal observation; Figure 7). Unfortunately, providing mice with the opportunity for tunnelling can make them rather difficult to catch although they will often sleep in an attached cage that leads to the tunnelling substrate. However, if regular handling is not required, or naturalistic behaviour is desirable, several centimetre deep, suitable substrate [e.g., damped peat with rocks or fibrous bedding to support the tunnel system] provides for almost instantaneous digging and some very entertaining mouse behaviour. Wood chip bedding might be a suitable compromise as it allows mice to perform digging behaviour and seek a darker environment but does not allow them to totally escape detection from human concerns. Surrogate burrows can be offered in the form of plastic tubes designed for pet rodents; several types are available commercially.

Laboratory mice seem to gain a great sense of security in these tunnels even when they are transparent; they often appear completely oblivious to nearby human presence. Providing tubes as tunnels can also make catching the mice a little difficult, although the tunnels can usually be separated into smaller sections and the one containing the mouse placed into the cage he or she is being transferred to; the mouse then usually walks out of the tube within a few seconds. Alternatively, if there are short tubes, mice use these as retreats and run into them during attempted capture. The tube containing the mouse is then easily transferred elsewhere, or the protruding tail of the mouse used for quick and easy handling, which also reduces stress caused to the mouse.

Figure 7. Laboratory mice who have never encountered deep substrate will readily dig tunnels when given the opportunity.

As described before, commercial pet companies produce "mazes" for pet rodents that might provide a practical surrogate tunnel system for laboratory mice in some situations.

Chewing/gnawing

Mice will readily chew on a variety of objects and should be provided with the opportunity to express this behaviour. Such chewable objects might include cardboard tubes, softwood blocks, old plastic water bottles, hay, straw, etc. (Figure 8). Cardboard tubes are particularly versatile as they also provide opportunities for shelter, climbing and manipulation.

Figure 8. This enrichment is advertised as a wooden chewing block, but its design allows it to also be used as a nest/shelter (the mice drag paper into it), and a climbing object.

Thermoregulation

Some rodents prefer cooler ambient temperatures in the dark phase and warmer temperatures during the light phase (Gordon, 1993). This suggests that a diurnally changing temperature might contribute to improving the animals' comfort. Of course, providing suitable nesting material is likely to circumvent the preference for changing ambient temperature and also provides the opportunity for other behaviours. Where metal cages are used, the "coldness" of this material can be overcome at least partly by provision of much bedding and nesting material.

Eliminative behaviour

Laboratory mice will often deposit their faeces in specific sites or latrines (Sherwin, 1996b; Blom, 1993; Figure 9). This behaviour could be involved in signals for social communication, hiding from potential predators, or it could simply be a hygiene response. Whichever, the small, featureless environment of a standard cage gives a mouse little choice to select certain areas or to avoid those marked by other individuals. Providing objects that are easily demarcated, such as vertical dividers, tins, jars, etc., will allow mice to show this eliminative behaviour pattern.

Figure 9. Mice will sometimes defecate in highly localised areas. This behaviour can be promoted by giving the mice a demarcated area, such as the petri-dish in the corner of this cage. The other object is an activity dish.

Social behaviour

Mice are a highly social species and, where possible, should be maintained in stable, harmonious groups. There are sound scientific and welfare reasons for this. Individual housing can influence responses to laboratory procedures (Mackintosh, 1962), and mice generally show clear preferences to be in close proximity to other mice, even males who have been housed singly (Vandenbroek et al., 1993; van Loo et al., 2001).

Forming groups: It seems a good general principle to form groups from weanlings who know each other. Same-sex groups are best set up before the animals reach the age of puberty. The likelihood of aggressive incompatibility increases in older animals, especially unfamiliar males (Barnard et al., 1991). When forming groups, various factors must be considered such as sex, age, reproductive condition, etc. Groups should be established in clean cages, as home-cage odour cues induce residents to attack intruders, and unfamiliar odours can increase aggression amongst the residents (Brown, 1985). It is generally not good practice to take mice from non-enriched cages and form new groups in enriched cages as this can result in territorial, aggressive disputes (McGregor and Ayling, 1990).

Maintenance of groups: Mice form a complex social organisation, and each animal plays a role in it, sometimes dependent on factors including age, sex, position in the hierarchy, or reproductive condition (Jennings et al., 1998). Upsetting this organisation by addition or removal of individuals, perhaps only one, can have considerable consequences that might ultimately affect the welfare of all mice within the group. There is generally no problem in group-housing young mice and non-breeding females. Housing mature males together is more of a problem, especially in smaller groups of two or three, which can put excessive amounts of stress on the subordinate animal(s). Aggression levels depend on a great many factors such as age, group size, cage size, previous experience of the animals and the situation (Jennings et al., 1998). The provision of cornhusk can buffer aggressive tension by offering subordinate animals cover and escape routes (Armstrong et al., 1998). Dominant males tend to be more aggressive in an environment with familiar odour than in a strange environment. Complete cage cleaning - new cage and new substrate - can, therefore, minimise aggression among male mice compared to partial cage cleaning (Gray and Hurst, 1995). Van Loo et al., (2000) observed that transferring nesting material during cage cleaning reduced aggression among males, whereas transferring sawdust containing urine and faeces seemed to intensify aggression.

It has been reported that providing enrichments or cage "furniture" for group-housed mice can increase aggression (McGregor and Ayling 1990; Haemisch et al., 1994). It was noted in one of these papers (McGregor and Ayling, 1990) that the mice might easily have regarded these objects as resources and thus defended them. Whilst trying to avoid being dismissive of these papers, the authors have assumed that sufficient space and refuges were provided for subordinate animals to show appeasement behaviour, escape, etc. Whenever enrichments are offered to mice, these should be in sufficient number and at a sufficient distance so that aggressive competition is not triggered.
 

In providing comfortable quarters for mice, there are several "-isms" we should avoid. We should avoid speceisism and remember there is no evidence to suggest that mice do NOT have the same capacity to suffer as other vertebrates, although their suffering might occur in different ways. We should also avoid anthropomorphism and anthropocentrism, and try to understand the mouse's world from it's own perspective, rather than our own human concerns. We should also avoid sizeism: simply because laboratory mice are small and can all appear to be the same [at least to us], this does not mean they have any less capacity to suffer as individuals.

In promoting appropriate housing for mice, it can be helpful to think in terms of optimising the 2 Qs: Quantity of space and Quality of space. We should be aiming to provide mice with the appropriate amount of space containing the appropriate diversity of environment that takes into account their species-specific characteristics and needs.
 

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Dr Chris Sherwin gained his Ph.D. at Murdoch University (Australia) in 1987 and after a period working in New South Wales, he moved to the University of Bristol (UK) in 1990. Since then, he has worked on a variety of subjects relating to animal behaviour and welfare. These include applied investigations of improved housing for layer hens, laboratory mice and turkeys, and more fundamental studies on social learning, motivation and preference tests. He is currently the UFAW Research Fellow in Animal Welfare and is investigating designs of cage to improve the welfare of laboratory mice.

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