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. 
Kammertoens, T., Jeuthe, S., Baranzke, H. et al. 2021. Breeding and maintenance of immunodeficient mouse lines under SPF conditions—A call for individualized severity analyses and approval procedures. Animals 11(6), 1789.

In the EU, the breeding of genetically modified laboratory animals is, by definition, an animal experiment if the offspring may experience pain, suffering, or harm. In order to determine the actual burden of genetically modified...

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...

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...

Buckinx, A., Van Schuerbeek, A., Bossuyt, J. et al. 2021. Exploring refinement strategies for single housing of male C57BL/6JRj mice: Effect of cage divider on stress-related behavior and hypothalamic-pituitary-adrenal-axis activity. Frontiers in Behavioral Neuroscience 15, 743959.

Introduction: Single housing of laboratory mice is a common practice to meet experimental needs, or to avoid intermale aggression. However, single housing is considered to negatively affect animal welfare and may compromise the scientific validity...

da Silva Medeiros Elidio, H., Coelho, J. W. R., Cavalcanti Pereira da Silva, L. C. et al. 2021. Housing density and aggression in Syrian hamsters. JAALAS 60(5), 506-509.

The Syrian hamster (Mesocricetus auratus) is a solitary and naturally territorial animal, with female hamsters being more aggressive than males. This behavior makes handling difficult because they are usually housed in groups, which can lead...

Locklear, J., Whiteside, T. E. 2021. Optimal colloidal water gel type and novel placement for frequent travelers. Laboratory Animal Science Professional 9(6) (November/December), 38-40.

During transportation, animals must have a water source available to prevent dehydration. Some shipping facilities use potatoes whereas, others use colloidal water gels that provide a uniform water source. The problem occurs when colloidal water...

Redaelli, V., Bosi, A., Luzi, F. et al. 2021. Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study. PLOS ONE 16(11), e0259938.

Background: Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those...

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...

Peterman, J.L., White, J.D., Calcagno, A. et al. 2020. Prolonged isolation stress accelerates the onset of Alzheimer’s disease-related pathology in 5xFAD mice despite running wheels and environmental enrichment. Behavioural Brain Research 379, 112366.

Research has demonstrated that stress can exacerbate AD pathology in transgenic mouse models of AD. The purpose of the present studies was to extend this work by determining whether a social stressor, isolation stress, would...

Talbot, S. R., Biernot, S., Bleich, A. et al. 2020. Defining body-weight reduction as a humane endpoint: A critical appraisal. Laboratory Animals 54(1), 99–110.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct...

Reading, P., Reading, R., Branstone, C. 2020. Mirror, mirror, on the wall. Animal Technology and Welfare 19(1), 98-100.

When mice are grouped together for the first time, it is a novel experience filled with new sights and smells that will stress the animal too much and may cause aggression. By adding a mirror...

Nwagwu, C. D., Defensor, E., Jiang, M. Y. et al. 2020. Endpoint in ovarian cancer xenograft model predicted by nighttime motion metrics. Lab Animal 49(8), 227–232.

Despite several therapeutics showing promise in nonclinical studies, survival from ovarian cancer remains poor. New technologies are urgently needed to optimize the translation of nonclinical studies into clinical successes. While most nonclinical settings utilize subjective...

Aleström, P., D’Angelo, L., Midtlyng, P. J. et al. 2020. Zebrafish: Housing and husbandry recommendations. Laboratory Animals 54(3), 213–224.

This article provides recommendations for the care of laboratory zebrafish (Danio rerio) as part of the further implementation of Annex A to the European Convention on the protection of vertebrate animals used for experimental and...

Wilkinson, M. J. A., Selman, C., McLaughlin, L. et al. 2020. Progressing the care, husbandry and management of ageing mice used in scientific studies. Laboratory Animals 54(3) 225–238.

Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about ‘healthy ageing’, ageing mice are being used increasingly in scientific research. Many departments and institutes involved with...

Kersemans, V., Wallington, S., Allen, P. D. et al. 2020. Manganese-free chow, a refined non-invasive solution to reduce gastrointestinal signal for T1-weighted magnetic resonance imaging of the mouse abdomen. Laboratory Animals 54(4), 353–364.

Commercial mouse chow is designed to provide a complete, nutrient-rich diet, and it can contain upwards of 100 mg/kg manganese, an essential mineral. Manganese acts as a relaxation time-shortening contrast agent for both T1 and T2...

Mendonça Soares, S., Kirsten, K., Pompermaier, A. et al. 2020. Sex segregation affects exploratory and social behaviors of zebrafish according to controlled housing conditions. Physiology & Behavior 222, 112944.

Zebrafish has become an animal model in research and articles have established ideal conditions for their maintenance. However, little is known regarding the influence of gender and other cues on zebrafish behavior. Thus, here we...

Hohlbaum, K., Frahm, S., Rex, A. et al. 2020. Social enrichment by separated pair housing of male C57BL/6JRj mice. Scientific Reports 10, 11165.

Laboratory male mice are often housed individually due to aggressive behavior or experimental requirements, though social isolation can cause welfare issues. As a strategy to refine housing of male mice, we introduce the separated pair...

Bailoo, J. D., Voelkl, B., Varholick, J. et al. 2020. Effects of weaning age and housing conditions on phenotypic differences in mice. Scientific Reports 10, 11684.

Poor reproducibility is considered a serious problem in laboratory animal research, with important scientific, economic, and ethical implications. One possible source of conflicting findings in laboratory animal research are environmental differences between animal facilities combined...

Zhang, X., Kumstel, S., Tang, G. et al. 2020. A rational approach of early humane endpoint determination in a murine model for cholestasis. ALTEX 37(2), 197-207.

Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Larson, M. A. 2020. Alternatives to shipping live mice. Laboratory Animal Science Professional 8(5) (September/October), 52-54.

Many in the lab animal field are familiar with shipping animals from vendor to investigator, from investigator to vendor, and from investigator to investigator. Sharing mouse models represents being good stewards of our animal resources...

Bodden, C., Wewer, M., Kästner, N. et al. 2021. Not all mice are alike: Mixed-strain housing alters social behaviour. Physiology & Behavior 228, 113220.

The use of millions of mice in scientific studies worldwide emphasises the continuing need for a reduction of sample sizes, however, not at the expense of scientific validity. Split-plot designs have been suggested to enhance...

Shelton, D. S., Shelton, S. G., Daniel, D. K. et al. 2020. Collective behavior in wild zebrafish. Zebrafish 17(4), 243-252.

Anthropogenic change is expected to alter environments at alarming rates. To predict the impact of modified environments on social behavior, we must study the relationship between environmental features and collective behavior in a genetically tractable...