Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Cait, J., Cait, A., Scott, R. W. et al. 2022. Conventional laboratory housing increases morbidity and mortality in research rodents: Results of a meta-analysis. BMC Biology 20(1), 15.

Over 120 million mice and rats are used annually in research, conventionally housed in shoebox-sized cages that restrict natural behaviours (e.g. nesting and burrowing). This can reduce physical fitness, impair thermoregulation and reduce welfare (e.g...

Brough, D. W., Murkin, J. T., Amos, H. E. et al. 2022. Comparing variability in measurement of subcutaneous tumors in mice using 3D thermal imaging and calipers. Comparative Medicine 72(6), 364–375.

Repeatable tumor measurements are key to accurately assessing tumor growth and treatment efficacy. A preliminary study that we conducted showed that a novel 3D and thermal imaging system (3D-TI) for measuring subcutaneous tumors in rodents...

Zeng, Y., Jin, H., Wang, J. et al. 2022. An optimized method for intratracheal instillation in mice. Journal of Pharmacological and Toxicological Methods 118, 107230.

Non-invasive intratracheal instillation is an important method for direct exposure of the respiratory tract which is commonly used in toxicology, environmental science, and other research fields. However, there is no standard operating process for non-invasive...

Atkinson, J., Boden, T., Mocho J.-P. et al. 2021. Refining the unilateral ureteral obstruction mouse model: No sham, no shame. Laboratory Animals 55(1), 21-29.

Fibrosis, as a common final pathway in many renal diseases, contributes significantly to the decline of organ function and to progression to end-stage renal disease. To establish therapeutic interventions that target fibrosis, animal models are...

Justin, M., Jež, M., Košir, A. et al. 2021. Application of the 3R principles: Vertebrae as an additional source of murine bone-marrow cells. Laboratory Animals 55(1), 43-52.

Experimental murine models are an essential tool in the field of bone marrow (BM) transplantation research. Therefore, numerous mice are required to obtain a sufficient number of BM cells, which is in contrast with the...

Sørensen, D., Cloutier, S., Gaskill, B. (Eds.). 2021. Animal-centric Care and Management - Enhancing Refinement in Biomedical Research. CRC Press, Boca Raton, FL.

The concept of the 3Rs (Refinement, Reduction and Replacement) has been used as a framework for improving the welfare of laboratory animals for the last half century. By establishing an animal-centric view on housing and...

Giménez-Llort, L., Torres-Lista, V. 2021. Social nesting, animal welfare, and disease monitoring. Animals 11(4), 1079.

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored...

Vis, A., Lammers, J. C. A. M., de Vroege, R. et al. 2021. Strategies to improve survival from surgery for heart valve implantation in sheep. Comparative Medicine 71(3), 235-239.

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by...

Perea, C., Vázquez-Ágredos, A., Ruiz-Leyva, L. et al. 2021. Caloric restriction in group-housed mice: Littermate and sex influence on behavioral and hormonal data. Frontiers in Veterinary Science 8, 639187.

Much of the research done on aging, oxidative stress, anxiety, and cognitive and social behavior in rodents has focused on caloric restriction (CR). This often involves several days of single housing, which can cause numerous...

Xu, J. J., Thurston, S. E., Robinson, T. J. et al. 2021. Effects of analgesics on tumor growth in mouse models of prostate cancer bone metastasis. JAALAS 60(3), 341-348.

Murine models of tumor development often require invasive procedures for tumor implantation, potentially causing pain or distress. However, analgesics are often withheld during implantation because of concerns that they may adversely affect tumor development. Previous...

Koch, A. L., Rusnak, M., Peachee, K. et al. 2021. Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice. Laboratory Animals 55(2), 142-149.

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these...

Xie, W., Kordt, M., Palme, R. et al. 2021. Diagnostic ability of methods depicting distress of tumor-bearing mice. Animals 11(8), 2155.

Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized...

Xie, W., Palme, R., Schafmayer, C. et al. 2021. Distress analysis of mice with cervical arteriovenous fistulas. Animals 11(11), 3051.

The welfare of laboratory animals is a consistent concern for researchers. Its evaluation not only fosters ethical responsibility and addresses legal requirements, but also provides a solid basis for a high quality of research. Recently...

Garcia, T., Brown, C., Margolies, D. et al. 2021. Grinding on a last nerve: Attempting to curb food grinding in mice. Laboratory Animal Science Professional 9(6) (November/December), 34-36.

Food grinding, or chewing food without ingestion, is a topic of interest in the laboratory animal community. In addition to increased effort needed to deal with this excess waste and provide suitable microenvironment for animals...

Winn, C. B., Hwang, S. K., Morin, J. et al. 2021. Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models. PLOS ONE 16(9), e0257694.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying...

Miller, A. L., Roughan, J. V. 2021. Welfare assessment, end-point refinement and the effects of non-aversive handling in C57BL/6 mice with Lewis lung cancer. Animals 12(1), 23.

Cancer-bearing mice are at risk of developing anxiety, pain, or malaise. These conditions may not only harm welfare but could also undermine data quality and translational validity in studies to develop therapeutic interventions. We aimed...

Weegh, N., Zentrich, E., Zechner, D. et al. 2021. Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model. PLOS ONE 16(12), e0261662.

Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore...

Verjat, A., Devienne, P., Rödel, H. G. et al. 2021. More exploratory house mice judge an ambiguous situation more negatively. Animal Cognition 24(1), 53–64.

Exploration tendency, one of the most investigated animal personality traits, may be driven by either positive (when seeking interesting information) or negative (to reduce the uncertainty of the environment) affective/emotional profiles. To disentangle the valence...

Wolfoviz-Zilberman, A., Houri-Haddad, Y., Beyth, N. 2021. A novel dental caries model replacing, refining, and reducing animal sacrifice. Applied Sciences 11(15), 7141.

In vitro and in vivo models simulating the dental caries process enable the evaluation of anti-caries modalities for prevention and treatment. Animal experimentation remains important for improving human and animal health. Nonetheless, reducing animal sacrifice...

Schneider, L., Kemper, N., Spindler, B. 2020. Stereotypic behavior in fattening bulls. Animals 10(1), 40.

The occurrence of stereotypies in captive animals may indicate restrictions in animal welfare. In cattle, common stereotypies are tongue playing, manipulation of objects, or conspecifics. However, to our knowledge, the occurrence of stereotypies in fattening...

Neave, H. W., Costa, J. H. C., Weary, D. M. 2020. Long-term consistency of personality traits of cattle. Royal Society Open Science 7(2), 7191849.

Personality is often defined as the behaviour of individual animals that is consistent across contexts and over time. Personality traits may become unstable during stages of ontogeny from infancy to adulthood, especially during major periods...

Nøgaard, S. A., Sand, F. W., Sørensen, D. B. et al. 2020. Four- and six-hour urinary albumin excretion is a valuable alternative to 24-h urinary albumin excretion in male db/db mice. Animal Welfare 29(2), 143-149.

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic...

Mallien, A. S., Häger, C., Palme, R. et al. 2020. Systematic analysis of severity in a widely used cognitive depression model for mice. Laboratory Animals 54(1), 40–49.

Animal models in psychiatric research are indispensable for insights into mechanisms of behaviour and mental disorders. Distress is an important aetiological factor in psychiatric diseases, especially depression, and is often used to mimic the human...

Weegh, N., Füner, J., Janke, O. et al. 2020. Wheel running behaviour in group-housed female mice indicates disturbed wellbeing due to DSS colitis. Laboratory Animals 54(1), 63–72.

Voluntary wheel running (VWR) behaviour is a sensitive indicator of disturbed wellbeing and used for the assessment of individual experimental severity levels in laboratory mice. However, monitoring individual VWR performance usually requires single housing, which...

Chartier, L. C., Hebart, M. L., Howarth, G. S. et al. 2020. Affective state determination in a mouse model of colitis-associated colorectal cancer. PLOS ONE 15(1), e0228413.

Behavioural indicators of affective state, including burrowing, clinical scores and the Mouse Grimace Score have not yet been validated in mouse models of chronic gastrointestinal disease. Additionally, a comparison of these methods has not been...