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. 
Hickman, D. L. 2023. Euthanasia of neonatal rats and mice using carbon monoxide. JAALAS 62(3), 274–278.

Minimization of potential pain and distress of rodents undergoing euthanasia is a touchstone of veterinary clinical medicine. Evaluation of this issue in postweanling rodents has supported revisions to the AVMA (American Veterinary Medical Association) Guidelines...

Stuckey, J. E., Makhija, S. D., Reimer, D. C. et al. 2023. Effects of different grades of carbon dioxide on euthanasia of mice (Mus musculus). JAALAS 62(5), 430–437.

Carbon dioxide (CO2) is a conditionally acceptable method for mouse euthanasia, according to the American Veterinary Medical Association Guidelines for the Euthanasia of Animals. In a 2012 Office of Laboratory Animal Welfare (OLAW) webinar, representatives...

Guillaumin, A., Vlcek, B., Wallén-Mackenzie, Å. 2022. Improving well-being and survival in the 6-OHDA lesion model of Parkinson´s disease in mice: Literature review and step-by-step protocol. Scandinavian Journal of Animal Science 48(1), 1-21.

Parkinson’s disease (PD) is the most common neurodegenerative motor disorder and primarily affects movement control but also a range of non-motor functions. With unknown etiology and lack of cure, much research is dedicated to unravel...

Hickman, D. L. 2022. Minimal exposure times for irreversible euthanasia with carbon dioxide in mice and rats. JAALAS 61(3), 283-286.

When using an anesthetic overdose to euthanize laboratory rodents, a secondary method of euthanasia is recommended to ensure that the apparent death is irreversible. This secondary method usually is accomplished through the collection of tissues...

McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.

Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...

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...

Clarkson, J. M., Martin, J. E., McKeegan, D. E. F. 2022. A review of methods used to kill laboratory rodents: Issues and opportunities. Laboratory Animals 56(5), 419-436.

Rodents are the most widely used species for scientific purposes. A critical pre-requisite of their use, based on utilitarian ethical reasoning, is the provision of a humane death when necessary for scientific or welfare grounds...

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...

MacLellan, A., Nazal, B., Young et al. 2022. Waking inactivity as a welfare indicator in laboratory mice: Investigating postures, facial expressions and depression-like states. Royal Society Open Science 9(11), 221083.

Animal welfare assessment relies on valid and practical indicators of affect. In mice, the most widely used research vertebrates, lying still with eyes open, inactive-but-awake (IBA) in the home cage, has potential to be one...

Novak, J., Jaric, I., Rosso, M. et al. 2022. Handling method affects measures of anxiety, but not chronic stress in mice. Scientific Reports 12(1), 20938.

Studies in mice have shown that less aversive handling methods (e.g. tunnel or cup handling) can reduce behavioural measures of anxiety in comparison to picking mice up by their tail. Despite such evidence, tail handling...

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...

Dickmann, J., Gonzalez-Uarquin, F., Reichel, S. et al. 2022. Clicker training mice for improved compliance in the catwalk test. Animals 12(24), 3545.

The CatWalk test relies on the run of mice across the platform to measure a constant speed with low variation. Mice usually require a stimulus to walk to the end of the catwalk. However, such...

Mieske, P., Hobbiesiefken, U., Fischer-Tenhagen, C. et al. 2022. Bored at home?—A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice. Frontiers in Veterinary Science 9, 899219.

Boredom is an emotional state that occurs when an individual has nothing to do, is not interested in the surrounding, and feels dreary and in a monotony. While this condition is usually defined for humans...

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...

Hickman, D. L. 2021. Wellbeing of mice euthanized with carbon dioxide in their home cage as compared with an induction chamber. JAALAS 60(1), 72-76.

The AVMA Guidelines on Euthanasia state that, to decrease potential distress of animals, the home cage should be used for the euthanasia of mice. The current study evaluated this recommendation by comparing behavioral and physiologic...

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...

Carbone, L. 2021. Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species. Scientific Reports 11(1), 493.

Alone among Western nations, the United States has a two-tier system for welfare protections for vertebrate animals in research. Because its Animal Welfare Act (AWA) excludes laboratory rats and mice (RM), government veterinarians do not...

Krakenberg, V., Wewer,M., Palme, R. et al. 2021. Regular touchscreen training affects faecal corticosterone metabolites and anxiety-like behaviour in mice. Behavioural Brain Research 401, 113080.

Automated touchscreen techniques find increasing application for the assessment of cognitive function in rodents. However, hardly anything is known about the potential impact of touchscreen-based training and testing procedures on the animals under investigation. Addressing...

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...

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...