Acclimating Research Animals Through Effective Nurturing

Stress in Mouse Research Models

Not all mouse strains will experience and display stress in the same ways. Males and females differ in their baseline stress markers, inbred rodent strains differ in most behavioral responses to stress, and genetically engineered models could respond in varying ways depending on the type of mutation(s) they carry1.

Inducing Stress by Over-Nurturing

A new cohort of research models is exciting, and the researchers involved might want to study the new animals very carefully once they arrive at their facility to ensure they are eating, drinking, and not displaying any signs of illness. While visual monitoring and inspections are beneficial, certain behaviors associated with monitoring their health can induce stress in the animal.

The amount of handling a mouse experiences is a key contributing factor to increased stress levels. Ideally, mice should be handled as little as possible and kept in the same room for the duration of their stay in your facility. Moving mice to a new location, with different odors, air flow, and watering methods, further elevates stress levels in the animals.

Causes of Human Interaction-Induced Stress

Proper Enrichment Helps Animals Acclimate

Environmental enrichment, with regards to animal husbandry, refers to the addition of objects or changes in cage conditions that aim to improve the welfare of laboratory animals3. Many different kinds of enrichment are beneficial to the health and well-being of mouse models. Environmental enrichment enables the animals to express species-specific behaviors such as nesting, resting, exploring, foraging, and gnawing.

Nesting material is often considered the most important enrichment, as it allows mice to thermoregulate while they are resting and express their species-typical nesting behavior. Different kinds of paper, which may or may not be purchased pre-shredded, are some of the most popular choices, as well as cotton squares the animals can shred themselves.

Chew sticks, tubes, various types of huts, lofts, cage dividers and plastic u-shaped swings are other popular choices usually used in addition to nesting material. The super immunodeficient huNOG and huNOG-EXL mouse models have shown a positive response to enrichment provided by Shepherd shacks®. These paper structures allow the animals to hide and nest, and are also able to be safely broken down and chewed on4.

Proper Acclimation of Laboratory Mouse Models

Taconic Biosciences' veterinarian Dr. Julita Ramirez-Komo and veterinary nurse Emily Shako recommend a twelve-day acclimation period for research mice before starting any experiments. This helps the animals adapt to their new environment and reduces morbidity and mortality.

When necessary, handling should be slow and gentle, and animals should be housed on a lower part of the rack away from doors, traffic, and equipment such as biosafety cabinets or cage change stations.

The animals will also be transitioning over to water from gel hydration in transport. Automatic watering lixits should be regularly toggled, or easier 'training lixits' can be used to help the animals learn to drink from them. Supplemental gel hydration may be required while the animals are adjusting to drinking from the water source available at the customer's facility.

A gradual transition from their current feed to the customer's feed of choice is also recommended.

Additional Concerns for NOG Mice

Additionally, NOG portfolio models should be unpacked from the transport container immediately upon arrival at the facility by experienced animal care staff and carefully evaluated before being placed in housing. NOG mice which have been experimentally manipulated, such as via irradiation and engraftment of a human immune system (huNOG and huNOG-EXL), normally have a mild scruffy coat appearance, mild kyphosis, and pale integument which make the mice appear as hunched, scruffy, and pale. Even with these issues, the animals should still appear bright, alert, and active. If the animals appear slow, lethargic, and severely hunched and/or pale, veterinary staff should be contacted to evaluate the animals.

They should be offered a supplemental hydrogel, gel diet such as Nutra-Gel Diet™, or given sterile saline subcutaneously under direction from veterinary staff and reevaluated to determine if there has been improvement or of the animal is declining and should be euthanized.

References:

1. National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals. Recognition and Alleviation of Pain and Distress in Laboratory Animals. ILAR J. 33, 71-74 (1991)..
2. National Research Council (US) Committee on Recognition and Alleviation of Distress in Laboratory Animals. Recognition and Alleviation of Distress in Laboratory Animals. (National Academies Press, 2008). doi:10.17226/11931..
3. Bailoo, J. D. et al. Effects of Cage Enrichment on Behavior, Welfare and Outcome Variability in Female Mice. Frontiers in Behavioral Neuroscience 12, 232 (2018)..
4. Shepherd Specialty Papers. Shepherd Shack. Accessed: 4th January 2019..