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. 
Fehrenbach, L. A., Adekanye, A. A., Palillo, M. B. et al. 2022. Internal temperatures of packaging for overnight cross-country shipping of zebrafish (Danio rerio). Comparative Medicine 72(3), 195-203.

As the use of zebrafish (Danio rerio) as a research model continues to rise, so too will the shipping and sharing of zebrafish strains across collaborating institutions. If done incorrectly, shipping can result in significant...

O'Malley, C. I., Hubley, R., Tambadou, H. et al. 2022. Refining restraint techniques for research pigs through habituation. Frontiers in Veterinary Science 9, 1016414.

Pigs are common research models and are strong animals that can be difficult to restrain. Improper restraint can put pigs and research personnel at risk for injury and induce stress, which can affect research outcomes...

Barkus, C., Bergmann, C., Branco, T. et al. 2022. Refinements to rodent head fixation and fluid/food control for neuroscience. Journal of Neuroscience Methods 381, 109705.

The use of head fixation in mice is increasingly common in research, its use having initially been restricted to the field of sensory neuroscience. Head restraint has often been combined with fluid control, rather than...

Zevnik, B., Jerchow, B., Buch, T. 2022. 3R measures in facilities for the production of genetically modified rodents. Lab Animal 51(6), 162-177.

Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where...

Khalajzeyqami, Z., Grandi, A., Ferrini, E. et al. 2022. Pivotal role of micro-CT technology in setting up an optimized lung fibrosis mouse model for drug screening. PLOS ONE 17(6), e0270005.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with no curative pharmacological treatment. The most used animal model of IPF for anti-fibrotic drug screening is bleomycin (BLM)-induced lung fibrosis. However, several issues have been reported...

Chen, J., Xu, X., Dalhaimer, P. et al. 2022. Tetra-primer amplification-refractory mutationsystem (ARMS)—PCR for genotyping mouse leptin gene mutation. Animals 12(19), 2680.

Due to spontaneous deficiency in leptin, ob/ob mice are one of the most commonly used experimental animal models in diabetes research. In this study, we reported a quick and easy-to-conduct genotyping method using tetra-primer amplification...

Chen, T., Zhou, Z.-Y., Liu, J.-Y. et al. 2022. Impact of partial bile duct ligation with or without repeated magnetic resonance imaging examinations in mice. Scientific Reports 12(1), 21014.

Partial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects...

Coutant, M., Malmkvist, J., Kaiser, M. et al. 2022. Piglets’ acute responses to local anesthetic injection and surgical castration: Effects of the injection method and interval between injection and castration. Frontiers in Veterinary Science 9, 1009858.

Although applied in some countries, efficacy of local anesthetics based on procaine to mitigate acute responses to piglet castration remains questioned. This paper presents results from a factorial study examining the effects of two methods...

Fink, L. B., Mukobi, A., Gruber, L. et al. 2022. Longitudinal analysis of variability in fecal glucocorticoid metabolite concentrations in three orangutans (Pongo pygmaeus pygmaeus and Pongo pygmaeus abelii) before, during, and after transition from a regular habitat environment to temporary housing in indoor holding facilities. Animals 12(23), 3303.

Considerable research has been conducted on the effects of inter-institutional transfers, but far less consideration has been given to intra-institutional transfers and extended housing in off-habitat holding. On 15 May 2018, The Oregon Zoo’s orangutans...

O’Malley, C. I., Hubley, R., Tambadou, H. et al. 2022. Refining restraint techniques for research pigs through habituation. Frontiers in Veterinary Science 9, 1016414.

Pigs are common research models and are strong animals that can be difficult to restrain. Improper restraint can put pigs and research personnel at risk for injury and induce stress, which can affect research outcomes...

Söbbeler, F. J., Wendt, S., Briese, A. et al. 2022. Comparative study of pain-related responses of male piglets up to seven days of age to the application of different local anaesthetics and subsequent castration. Animals 12(20), 2833.

To evaluate pain responses to intratesticular and subscrotal injection of three local anaesthetics and their efficacy during castration a randomized controlled study was conducted. In groups of 20 piglets, procaine (2%), lidocaine (2%), or mepivacaine...

Weisskopf, M., Glaus, L., Trimmel, N. E. et al. 2022. Dos and don’ts in large animal models of aortic insufficiency. Frontiers in Veterinary Science 9, 949410.

Aortic insufficiency caused by paravalvular leakage (PVL) is one of the most feared complications following transcatheter aortic valve replacement (TAVI) in patients. Domestic pigs (Sus scrofa domestica) are a popular large animal model to study...

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...

Skade, L., Kristensen, C. S., Nielsen, M. B. F. et al. 2021. Effect of two methods and two anaesthetics for local anaesthesia of piglets during castration. Acta Veterinaria Scandinavica 63, 1.

Since January 2019, surgical castration of male piglets must be performed using local anaesthesia, if farmers deliver pigs to the primary exporting slaughterhouses according to the “Danish quality scheme”; a voluntary initiative taken by the...

Ramos, J., Balasch, J. C., Tort, L. 2021. About welfare and stress in the early stages of fish. Frontiers in Veterinary Science 8, 634434.

In conclusion, the investigations carried out up to now demonstrate that during the early stages fish show high sensitivity to many types of stressors involving an array of responses to overcome alterations that could affect...

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...

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...

Steagall, P. V., Bustamante, H., Johnson, C. B. et al. 2021. Pain management in farm animals: Focus on cattle, sheep and pigs. Animals 11(6), 1483.

Pain causes behavioral, autonomic, and neuroendocrine changes and is a common cause of animal welfare compromise in farm animals. Current societal and ethical concerns demand better agricultural practices and improved welfare for food animals. These...

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...

Labitt, R. N., Oxford, E. M., Davis, A. K. et al. 2021. A validated smartphone-based electrocardiogram reveals severe bradyarrhythmias during immobilizing restraint in mice of both sexes and four strains. JAALAS 60(2), 201-212.

Mouse handling and restraint affect behavior, physiology, and animal welfare, yet little information is available on how various mouse restraint methods affect cardiovascular parameters. We validated the use of a smartphone-based ECG sys- tem in...

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...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

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...