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Animal Source

Spring 2017 ARP newsletter

Volume 15, Issue 2

 

Managing Mouse Aggression

Unchecked aggression can lead to injuries, pain, distress and suffering in laboratory mice. Males are typically responsible for most agonistic encounters with genetics and environment playing a role in the frequency and intensity of aggressive behaviors. While individual housing of male mice will prevent aggressive interactions, mice are a social species and solitary housing has been shown to lead to detrimental physiological and psychological effects due to stress. By understanding why mice behave as they do, we may be able to reduce aggression while allowing social interaction in males.

Mouse social structure is complex and includes various types of agonistic behaviors. “Mediated aggression” serves to solidify dominance hierarchies while avoiding fighting and includes activities such as mounting of a subordinate male by a dominant male. “Escalated aggression” generally results when mediated aggression either fails or is absent. Escalated aggression includes attack and other fighting behaviors which can lead to serious injury or death. In wild mice, an attack by a territory owner is usually followed by the intruder fleeing. The territory owner usually stops chasing the intruder once the line of sight is broken or the intruder exits the territory.
Although laboratory mice have been domesticated and genetic background influences expression, they retain many of these behavioral characteristics. Male laboratory mice housed in cages will actively defend their “territory”. Unfortunately for other males housed in the same cage, there is no place to flee from an aggressive mouse and so attacks may be frequent and prolonged with dire consequences.

There are management strategies that may be used to reduce serious aggression in male mice. If males are to be housed together, initially combine small groups (3-4 mice; littermates if possible) at 3-4 weeks of age (prior to puberty). Once mice reach puberty, do not add or subtract mice from the group as this will lead to fighting. Males can sometimes be successfully housed together in small groups well into adulthood, especially if they are not exposed to female pheromones (released by females in the same room) or extensively manipulated. However, groups must be monitored and separated if fighting leads to injuries.

The provision of nesting material has been shown to reduce aggressive interactions and provide male mice with both “something to do” and the ability to build a nest (a robust behavior in mice). Whatever material is used, a sufficient amount must be provided to allow the mice to actually create a nest and the material should be transferred to the new cage during cleaning. Rigid shelters, such as hard plastic boxes or even running wheels have been shown to increase aggression in some studies. It’s possible that shelters or other solid objects may be perceived as a resource that the dominant mouse must defend and they are not recommended for male groups. Some claims have been made that providing dividers within the cage, allowing subordinate mice to visually escape from the dominant mouse, can significantly reduce fighting. At least one lab animal products company is reported to be planning to market a cage divider in the near future.

In the event that fighting occurs, males must be separated. Attempting to maintain groups that are fighting will result in not only injuries, but all of the mice in the cage will be under serious stress that will affect their physiology and behavior making them poor experimental subjects. For more information on this topic, please see the reference listed below.


Gaskill B. Aggression in Laboratory Mice: Potential Influences and How to Manage It. The Enrichment Record, Winter 2014. http://enrichmentrecord.com/wp-content/uploads/2014/01/AGGRESSION-IN-LAB-MICE.pdf

Considerations in the Administration of Substances to Research Animals

When formulating experimental substances to be administered to animals it is important to consider the physiochemical properties of the substance and choose an appropriate dosing vehicle, volume and route of administration to ensure the welfare of the animal and accuracy of the results. Below are listed some general guidelines to help investigators in this task. More information may be obtained from the reference listed below or an ARP veterinarian.

Solvents for solutions

Physiological saline (0.9% NaCl)
Distilled water (sterile water for injection) – pain with subcutaneous injection; some hemolysis with intravenous injection.
Organic solvents – used for water-insoluble compounds. Suitable solvents should meet the following criteria:

  • No pharmacological effects
  • Stable under conditions of use
  • Non-toxic
  • Non-irritant
  • Non-sensitizing

Vegetable oils (e.g., peanut, olive) – suitable for lipid soluble substances

  • Absorption will be slowed
  • Cannot use for intravenous injection

Suspensions

Dosage will not be precise due to sedimentation of particles
If used for IV injection, the particles must be finely divided

Substance distribution in the body will not be uniform due to deposition of particles in the capillary beds of the extremities and lungs

Particle deposition in the lungs may result in pulmonary distress

pH and Volume

            Generally, a range of pH 4.5 – 8.0 is acceptable for all routes of administration.The amount of fluid that may be given at one time depends on the species and route of administration. Larger volumes may be divided between multiple sites for subcutaneous and intramuscular administration. Acceptable volume and rate for intravenous administration is dependent on factors such as pH, osmolarity and potential physiologic effects of the substance to be given.  In general, use the smallest volume possible after taking into consideration the solubility of the compound and ability to accurately measure the appropriate dosage.

Absorption

Substances with greater solubility are absorbed at a faster rate
The higher the concentration of a substance in solution, the faster the absorption rate.
The greater the area of absorbing surface, the faster the rate of absorption.

  • Intravenous administration = almost instantaneous absorption
  • Intraperitoneal absorption is about 4x slower than intravenous
  • Intramuscular absorption is faster than subcutaneous which is faster than oral absorption.

Reference:
Morton DB, et al. Refining procedures for the administration of substances. 2001 Laboratory Animals 35, 1-41.

Seoul Virus Infection in Rats and Humans

Earlier this year CDC officials began investigating an outbreak of Seoul virus infection that affected at least 17 people in 7 U.S. states. The infections were thought to have originated from home-based pet rat breeding operations. The CDC investigated facilities (homes or premises) in 15 states with 11 states reporting laboratory-confirmed Seoul virus positive results for humans or rats. Canadian health authorities also investigated Seoul virus infected facilities in Ontario with epidemiological links to US rat facilities. No human deaths were reported.

Seoul virus is a member of the hantavirus genus within the bunyavirus family and is known to cause hemorrhagic fever with renal syndrome (HFRS) in people worldwide. Although most human infections with Seoul virus occur in Asia and cause mild or no disease, approximately 1-2% of cases proceed to HFRS and death. As is typical with hantaviruses, Seoul virus is carried by rodents, specifically the Norway rat (Rattus norvegicus) and has been found in wild and pet rats around the world. Rats infected with Seoul virus do not show signs of illness. Infection in rats is thought to be lifelong with intermittent viral shedding. Transmission occurs via direct contact with urine, feces or saliva of infected rats or aerosolization of these materials.

Serologic testing of rats known to be linked to ratteries with confirmed Seoul virus infection was performed by the CDC. Although widespread testing of pet rats has not been recommended, the CDC has validated the IDEXX Opti-Spot Hantaan virus serology test to use for Seoul virus testing in rats. Other commercial laboratories also offer serology and PCR testing for hantaviruses although the CDC has not reported validation of these tests as of yet.

Employees of laboratory animal facilities are commonly instructed not to have contact with pet or wild rodents in an effort to prevent the introduction of pathogens such as Seoul virus into a facility. In addition to the potential infection of research rodents the Seoul virus outbreak highlights the zoonotic potential of some infectious agents. The CDC lists at least 25 infectious diseases transmittable to humans from rodents. These include viral and bacterial pathogens such as West Nile Virus and Murine Typhus. More information on rodent zoonotic diseases may be found on the CDC website (https://www.cdc.gov/rodents/index.html).

 

Allergies in Personnel Working With Laboratory Animals

One of the most important occupational health risks for people working with laboratory animals is the development of allergies to animal products such as fur, dander, saliva and urine. Workers may develop allergic responses to these products after months or years of exposure. Symptoms vary from sneezing and runny nose to coughing, wheezing and shortness of breath typical of asthma. Although anyone may develop allergies, workers with a previous history of allergies, especially to dogs or cats, have a higher risk or developing laboratory animal allergies.
Protect yourself from exposure to animal allergens by observing the following guidelines when working with animals.

  • Work in a ventilated hood or safety cabinet whenever possible.
  • Wear dedicated laboratory coats or gowns to protect your clothing from contamination by animal products. Don’t wear these lab coats/gowns outside the animal room.
  • Always wear latex or other type of disposable gloves when handling animals or animal equipment to reduce skin contact with animal products.
  • Keep your work area clean to reduce the chance of exposure to fur, urine or other potential allergens.

The diagnosis of animal allergies requires testing by a medical doctor. Symptoms of animal related allergies and asthma have the potential to become severe enough to require affected workers to change jobs. Prevention is the best medicine!

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The next mouse biomethodology class will be held from 1-4 pm on June 23, 2017. Please contact the ARP if you would like to attend.