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. 
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...

Tetlow, S. A. J., Brennan, M. L., Garcia-Ara, A. 2022. Welfare indicators for stunning versus non-stunning slaughter in sheep and cattle: A scoping review. Vet Record 191(6), e1739.

Background: While most cattle and sheep in the United Kingdom are stunned before slaughter, non-stun methods are permitted to supply meat to specific consumers. This study aimed to identify the existing literature that compared animal...

Córneo, E., Michels, M., Abatti, M. et al. 2022. Enriched environment causes epigenetic changes in hippocampus and improves long-term cognitive function in sepsis. Scientific Reports 12(1), 11529.

Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory...

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...

Chung, Y. H., Gulumian, M., Pleus, R. C. et al. 2022. Animal welfare considerations when conducting OECD test guideline inhalation and toxicokinetic studies for nanomaterials. Animals 12(23), 3305.

The OECD test guidelines for animal experiments play an important role in evaluating the chemical hazards. Animal tests performed using OECD guidelines, especially when the good laboratory practice (GLP) principle is applied, reduce the duplication...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

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...

Mayes, B. T., Tait, L. A., Cowley, F. C. et al. 2022. Stocking density, restricted trough space, and implications for sheep behaviour and biological functioning. Frontiers in Veterinary Science 9, 965635.

Stocking density and trough space allowance can potentially impact sheep welfare during live export voyages. The aim of this study was to assess the welfare implications for sheep housed at five allometric stocking densities, with...

Nuber, M., Gonzalez-Uarquin, F., Neufurth, M. et al. 2022. Development of a 3D simulator for training the mouse in utero electroporation. PLOS ONE 17(12), e0279004.

In utero electroporation (IUE) requires high-level training in microinjection through the mouse uterine wall into the lateral ventricle of the mouse brain. Training for IUE is currently being performed in live mice as no artificial...

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...

Navarro-Castilla, A., Garrido, M., Hawlena, H. et al. 2021. Non-invasive monitoring of adrenocortical activity in three sympatric desert gerbil species. Animals 11(1), 75.

The study of the endocrine status can be useful to understand wildlife responses to the changing environment. Here, we validated an enzyme immunoassay (EIA) to non-invasively monitor adrenocortical activity by measuring fecal corticosterone metabolites (FCM)...

Casey, K. M., Gore, F., Vilches-Moure, J. G. et al. 2021. Management of morbidity and mortality in a New Zealand white rabbit model of steroidinduced osteonecrosis of the femoral head. Comparative Medicine 71(1), 86-98.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a condition documented in humans and animals exposed to chronic steroid administration. The rabbit has become a preferred animal model for investigating the pathogenesis and treatment of...

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...

Améndola, L., Ratuski, A., Weary, D. M. 2021. Individual differences in rat sensitivity to CO2. PLOS ONE 16(1), e0245347.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in...

Blaney, A., Jampachaisri, K., Huss, M. K. et al. 2021. Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus). PLOS ONE 16(2), e0246213.

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in...

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...

Silva-Reis, R., Faustino-Rocha, A. I., Gonçalves, M. et al. 2021. Refinement of animal model of colorectal carcinogenesis through the definition of novel humane endpoints. Animals 11(4), 985.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid...

Chmurska-Gąsowska, M., Sowińska, N., Pałka, S. et al. 2021. Non-invasive measurement of thyroid hormones in domestic rabbits. Animals 11(5), 1194.

Thyroid hormones are essential for metabolism, energy homeostasis and reproduction. Hormones can be measured in various biological source materials: blood, feces, urine, saliva and others. The aim of our study was to verify usefulness of...

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...