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Considerations regarding aggression in mice.
While mice can be socially harmonious, there are times when they can display aggression. This applies to mice in nature or in captivity. When mice are group housed in the laboratory, aggression can be triggered which, up to a certain level, can be regarded as normal or natural. However, when aggressive interactions between cage mates cause severe injury and stress in the animals, it leads to negative effects both on the well-being of the animals (both dominant and subordinate) and on the validity of experimental results. Although mostly associated with males, females can also exhibit aggressive behavior.
Fighting between mice is often noted by specific signs of injury such as the presence of skin wounds on the back and tail, or as more general signs such as weight loss. Multiple cage mates can be injured, while one (dominant) animal may remain unharmed. Behavioral observations show animals performing threats, attack bites on the back and flank, often while vocalizing. The pattern of aggression in male mice consists of a series of bursts that are separated by periods of relative inactivity. The most prominent reaction to aggressive acts is an escape leap that becomes full flight in which fleeing opponents are chased. Frequently attacked mice display a defeat posture with limp forelimbs, upward angled head and retracted ears. Females defending their pups will mainly strike at head and snout. Aggression can also be exhibited as excessive barbering or whisker biting, shown as bald spots on cage mates. This last type of aggression is mainly seen in female animals.
Potential causes of aggression
Causality can be found in both management and genetics. Under laboratory conditions housing is usually arranged by gender, which contrasts the social organization of wild mice, as freely living (house-) mice are organized in a structure with one dominant male, several females, juveniles and probably a few subordinate males. The dominant male defends the territory of the group especially against other adult males. Under laboratory conditions, several adult males are often forced to cohabitate. Once male mice reach sexual maturity, territorial aggression increases. Exposure to female odors promotes aggression as males will compete for breeding opportunities.
Classic selection and strain comparisons show the heritability of aggressive behavior, and point to the influence of several genes. It can affect both inbred as well as outbred strains. Swiss outbred mice are
known to be highly aggressive. Some inbred strains are genetically predisposed to high levels of aggression (SJL, BALB/c).
Prevention of aggression
Some preventive measures can be taken to minimize triggering aggressive behavior. Cage cleaning can increase aggression in male groups due to the disruption of odors that normally define their social environment.8 Providing nesting material and transferring odor cues (non-soiled nesting material) during cage cleaning reduces aggression in some strains, but can increase aggression in others. Shelters
may influence aggressive behaviour, depending on i.e. number, size and design.Males should not be exposed to male urine when temporarily removed from their social groups and contamination of home cages with different scents should be avoided, for example, by cleaning cages thoroughly and ensuring that soiled substrate cannot fall into other cages.
It is not per se necessary to house male mice individually. Studies describe that male mice prefer each other’s company to individual housing.8 Groups of three were found to have the most stable dominance
hierarchy and show the least aggression between cage mates. As unfamiliar mice are less tolerant to each other than acquainted ones, it is recommended not to disturb the social groups. Aggression is also a common response to unpredictable situations, such as experimental or husbandry procedures to which an animal cannot anticipate (e.g. cage cleaning or human approach). In these instances, an animal may direct its energy into aggression against nearby animals.
Policy of Envigo RMS is to house male mice strains, where there may be a concern about aggression, in smaller, stable groups from a young age and not mix these animals during husbandry procedures. These
animals are packed for transportation per cage and not mixed. Envigo applies this practice based on the experience gained with them for various mouse stocks and strains globally. Envigo advises housing male
animals as they are received in their shipping cohorts. Even though preventive measures are taken it may be impossible to completely remove aggression between mice in the present way of housing laboratory mice.
What can you do?
- Order male animals young (e.g. at 4 wks) and keep in small stable groups (3-5 animals) after arrival
- House male animals preferably per shipping compartment and do not mix animals from different compartments
- Newly grouped animals will establish a new hierarchy and close observation is needed to intervene at an early stage should aggression occur
- House males in social groups before adulthood
- Avoid housing males near female cages and avoid (indirect) exposure to female scent (e.g. gloves, equipment)
- Avoid unpredictable stimuli
- Avoid contamination of the home cage with other male scents (e.g. bedding falling in)
- Transfer clean nesting material to the new cage to retain some familiar scent and allow territory remarking at a lower, less stressful level
- Wash the cage when removing bedding
- Familiarize animals with other scents used in procedures
Aggression is a natural occurring phenomenon, but can interfere with welfare of the animals and validity of test results. Be alert, so preventive measures can be taken, such as using small groups, use nesting material which is transferred at cage cleaning and prevent mixing of the animals and unpredictable situations.