Small Changes, Big Results

University of Guelph researcher Allison Bechard examines how weaning age influences the welfare of laboratory mice.

Laboratory mice are one of the most commonly used animals in biomedical research, meaning that relatively small changes to their early husbandry could have lasting effects on the health and well-being of millions of animals. The practice of early weaning, for example, can be a cause of stress for almost any animal, and it is typical for young mice in the laboratory. They are usually separated from their mothers at the age of 3 weeks, whereas they would not disperse in nature until about a month later.

Mouse pups are born in a highly immature state and depend completely on their mothers for survival. The standard management-imposed separation of the mother and young occurs during a fragile developmental period of neural and behavioral organization. Along with curtailed maternal care, modified social milieu due to early separation of the sexes is a consequence of disrupting the family unit at this age. These influential effects of maternal and social deprivation are often largely overlooked in relation to welfare and as factors in research results.

We weaned C57Bl6 (B6) and CD-1 litters at either the standard 21 days or the more naturalistic 35 days to investigate the effects of this artificial, premature disruption to the mother-young bond.  Offspring from 14 litters were screened for neophobia and anxiety (e.g. elevated plus-maze, open field, acoustic startle response) between 2 to 3 months of age, and for stereotypic behavior (e.g. bar mouthing, somersaulting) and alopecia at an age of 6 to 7 months. The hypothesis was that delaying weaning age would improve adult welfare. The chosen strains were two of the most commonly used inbred and outbred mouse lines, while selected behavioral parameters bridge the previously distinct fields of neuroscience and welfare.

Results indicate that delaying weaning reduces adult anxiety, as measured by an elevated plus-maze (p<0.05). In females, weaning at a later age seems to decrease the prevalence of both alopecia (p<0.01) and stereotypic behavior (p<0.1) in adulthood. There was also a 30 percent reduction in the acoustic startle responses for delay weaned mice (p<0.05), although these findings need to be replicated on a larger scale.

Overall, the results supported our hypothesis and were favorable toward weaning when the mice are 5 weeks old, compared to the 3 week standard imposed by most facilities. Preliminary data suggests that delaying weaning produces animals with lower levels of anxiety, abnormal behavior and alopecia. The data presented here should also encourage researchers not to underestimate the importance of the age at which young are separated from their mothers when measuring adult behavior.

Finally, weaning mice at an age closer to natural dispersal helps to develop a normal phenotype; it could potentially be further explored as a protective mechanism for enduring life in captivity and to reduce welfare problems in research animals. Later weaning is a simple, relatively low-cost manipulation of early husbandry that could be used to produce more stress-resistant phenotypes with better health and welfare. In collaboration with Jackson Laboratory, we are now working on replicating this work on a larger scale to provide the basis for future research into the effects of weaning age on welfare.

These studies were funded by the Animal Welfare Institute Refinement Awards and made possible through the generous support of an anonymous donor.

The Animal Welfare Institute thanks the following individuals for their assistance in reviewing the proposals submitted for the
2006 Refinement Awards:

Jas Barley, Southampton General Hospital

Lorraine Bell, University of Colorado Health Sciences

Lynette Chave, New South Wales Department of
Primary Industries

Alyssa Foulkes, University of Guelph

Roger Francis, University of Bristol School of Medical Sciences

Kay Steward, University of Notre Dame

Karolina Westlund, Stockholm University