FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units

FELASA working group on revision of guidelines for health monitoring of rodents and rabbits; Mähler (Convenor), M; Berard, M; Feinstein, R; Gallagher, A; Illgen-Wilcke, B; Pritchett-Corning, K; Raspa, M

doi:10.1177/0023677213516312

Cited by 648Animal testing and alternativesMicrobial infections and disease researchAnimal Behavior and Welfare Studies

FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units

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FELASA working group on revision of guidelines for health monitoring of rodents and rabbits, Mähler (Convenor), M, Berard, M, Feinstein, R, Gallagher, A, Illgen-Wilcke, B, Pritchett-Corning, K, Raspa, M·2014·Laboratory Animals

DOI 10.1177/0023677213516312

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Abstract

The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices.

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The animals' provenance, health or immune status, and history of previous testing or procedures can influence their physiology and behaviour, as well as their response to treatments, and thus impact on study outcomes.
“The animals’ provenance, their health or immune status, and their history of previous testing or procedures can influence their physiology and behaviour, as well as their response to treatments, and thus impact on study outcomes.”
From Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 (2020) · cites this paper as [112]
The paper’s introductory passage (indexed as Abstract; page not given) says infections can affect animals’ physiology, including behaviour and immune response, and can confound experimental results. Its health-monitoring discussion also considers immune status and the health history of the facility of origin. It does not establish that previous testing or procedures alter animals’ physiology, behaviour, or responses to treatments. (LLM, conf=0.85)
Experimental — accuracy not yet measured
The immune or microbiological status of the animals can influence welfare, experimental variability, and scientific outcomes.
“The immune or microbiological status of the animals can also influence welfare, experimental variability, and scientific outcomes [112–114].”
From Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 (2020) · cites this paper as [112]

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Blank, W. A., Henderson, K. S., & White, L. A. (2004) · Lab Animal · doi:10.1038/laban0204-26 · Cited by 28 · see citing works
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Patten, C. C., Myles, M. H., Franklin, C. L., & Livingston, R. S. (2010) · PubMed Central · Cited by 27 · see citing works
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Sorted by citations

Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0
Percie du Sert, N., Ahluwalia, A., Alam, S., Avey, M. T., Baker, M., Browne, W. J., Clark, A., Cuthill, I. C., Dirnagl, U., Emerson, M., et al. (2020) · PLOS Biology · doi:10.1371/journal.pbio.3000411 · Cited by 2,677 · see citing works
The 3Rs and Humane Experimental Technique: Implementing Change
Hubrecht, R. C., & Carter, E. (2019) · Animals · doi:10.3390/ani9100754 · Cited by 620 · see citing works
“, [2]) and environmental variables are better controlled, so more emphasis is usually placed on achieving Reduction through good and appropriate experimental design.”
Background
Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019Preprint
du Sert, N. P., Ahluwalia, A., Alam, S., Avey, M. T., Baker, M., Browne, W. J., Clark, A., Cuthill, I. C., Dirnagl, U., Emerson, M., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/703355 · Cited by 557 · see citing works
“The immune or microbiological status of the animals can also influence welfare, experimental variability and scientific outcomes [106-108].”
Background
Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence
Schaubeck, M., Clavel, T., Calasan, J., Lagkouvardos, I., Haange, S. B., Jehmlich, N., Basic, M., Dupont, A., Hornef, M., Bergen, M. V., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-309333 · Cited by 447 · see citing works
Large-scale two-photon calcium imaging in freely moving mice
Zong, W., Obenhaus, H. A., Skytøen, E. R., Eneqvist, H., de Jong, N. L., do Vale, R. D., Jorge, M., Moser, M., & Moser, E. I. (2022) · Cell · doi:10.1016/j.cell.2022.02.017 · Cited by 339 · see citing works
Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4+ T Cell Pathogenicity and Suppresses Autoimmunity
Angiari, S., Runtsch, M. C., Sutton, C. E., Pålsson‐McDermott, E. M., Kelly, B. L., Rana, N., Kane, H., Papadopoulou, G., Pearce, E. L., Mills, K. H. G., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.10.015 · Cited by 310 · see citing works
Of Mice, Dirty Mice, and Men: Using Mice To Understand Human Immunology
Masopust, D., Sivula, C. P., & Jameson, S. C. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700453 · Cited by 296 · see citing works
Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges
Perše, M., & Večerić‐Haler, Ž. (2018) · BioMed Research International · doi:10.1155/2018/1462802 · Cited by 247 · see citing works
“To avoid misinterpretation of the published results, research on animal models should be properly reported in accordance with the ARRIVE guidelines [195] or gold standard publication checklist [196], FELASA recommendations [197, 198], and standardized genetic nomenclature of rodents (http://www.”
Method
Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity
Alissafi, T., Kalafati, L., Lazari, M., Filia, A., Kloukina, I., Manifava, M., Lim, J.-H., Alexaki, V. I., Ktistakis, N. T., Doskas, T. K., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.07.001 · Cited by 196 · see citing works
Cisplatin Mouse Models: Treatment, Toxicity and Translatability
Perše, M. (2021) · Biomedicines · doi:10.3390/biomedicines9101406 · Cited by 141 · see citing works
Enhanced cultured diversity of the mouse gut microbiota enables custom-made synthetic communities
Afrizal, A., Jennings, S. A. V., Hitch, T. C. A., Riedel, T., Basic, M., Panyot, A., Treichel, N. S., Hager, F. T., Wong, E. O.-Y., Wolter, B., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.09.011 · Cited by 125 · see citing works
Standardised animal models of host microbial mutualism
Macpherson, A. J., & McCoy, K. D. (2014) · Mucosal Immunology · doi:10.1038/mi.2014.113 · Cited by 118 · see citing works
Combined Inhibition of TGF-β Signaling and the PD-L1 Immune Checkpoint Is Differentially Effective in Tumor Models
Sow, H. S., Ren, J., Camps, M. G. M., OSSENDORP, F. A., & ten Dijke, P. (2019) · Cells · doi:10.3390/cells8040320 · Cited by 112 · see citing works
“Animals tested negative for all agents listed in the Federation of European Laboratory Animal Science Associations (FELASA) guidelines for SPF mouse colonies [38].”
Heterochronic faecal transplantation boosts gut germinal centres in aged mice
Stebegg, M., Silva-Cayetano, A., Innocentin, S., Jenkins, T. P., Cantacessi, C., Gilbert, C., & Linterman, M. A. (2019) · Nature Communications · doi:10.1038/s41467-019-10430-7 · Cited by 107 · see citing works
Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation
Jirkof, P., Tourvieille, A., Cinelli, P., et al. (2014) · Laboratory Animals · doi:10.1177/0023677214562849 · Cited by 103 · see citing works
“The mice were free of all viral, bacterial, and parasitic pathogens listed in the FELASA recommendations, except for Helicobacter species.(28) All the animals were housed in groups of three to six animals for three weeks prior to testing in our animal room.”
Background
Facial Indicators of Positive Emotions in Rats
Finlayson, K., Lampe, J. F., Hintze, S., Würbel, H., & Melotti, L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0166446 · Cited by 99 · see citing works
CD3-Bispecific Antibody Therapy Turns Solid Tumors into Inflammatory Sites but Does Not Install Protective Memory
Benonisson, H., Altıntaş, I., Sluijter, M., Verploegen, S. A. B. W., Labrijn, A. F., Schuurhuis, D. H., Houtkamp, M., Verbeek, J. S., Schuurman, J., & van Hall, T. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0679 · Cited by 96 · see citing works
Towards a fully automated surveillance of well-being status in laboratory mice using deep learning: Starting with facial expression analysis
Andresen, N., Wöllhaf, M., Hohlbaum, K., Lewejohann, L., Hellwich, O., Thöne‐Reineke, C., & Belik, V. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228059 · Cited by 83 · see citing works
Mucin-2 knockout is a model of intercellular junction defects, mitochondrial damage and ATP depletion in the intestinal epithelium
Borisova, M. A., Achasova, K. M., Morozova, K. N., Andreyeva, E. N., Litvinova, E. A., Ogienko, A. A., Morozova, M. V., Berkaeva, M. B., Владимировна, К. Е., & Kozhevnikova, E. N. (2020) · Scientific Reports · doi:10.1038/s41598-020-78141-4 · Cited by 85 · see citing works
A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice
Silva-Cayetano, A., Foster, W. S., Innocentin, S., Belij-Rammerstorfer, S., Spencer, A. J., Burton, O. T., Fra-Bidó, S., Le Lee, J., Thakur, N., Conceicao, C., et al. (2021) · Med · doi:10.1016/j.medj.2020.12.006 · Cited by 84 · see citing works
Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain
Fornefett, J., Krause, J., Klose, K., et al. (2018) · BMC Microbiology · doi:10.1186/s12866-018-1186-8 · Cited by 81 · see citing works
“pneumotropica as an important pathogen in mice, rats and hamsters and recommends the examination every 3 months [16].”
Running in the wheel: Defining individual severity levels in mice
Häger, C., Keubler, L. M., Talbot, S. R., Biernot, S., Weegh, N., Buchheister, S., Büettner, M., Glage, S., & Bleich, A. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2006159 · Cited by 73 · see citing works
Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
Stebegg, M., Bignon, A., Hill, D. L., Silva-Cayetano, A., Krueger, C., Vanderleyden, I., Innocentin, S., Boon, L., Wang, J., Zand, M. S., et al. (2020) · eLife · doi:10.7554/elife.52473 · Cited by 76 · see citing works
Gnotobiotics: Past, present and future
Basic, M., & Bleich, A. (2019) · Laboratory Animals · doi:10.1177/0023677219836715 · Cited by 73 · see citing works
“Gnotobiotic mice should also be monitored for specific pathogens, for example those listed by the Federation of Laboratory Animal Science Associations (FELASA).(21,24) Viruses, except those included in the FELASA recommendations, are not specifically excluded from germ-free animals.”
Background
A genome-wide library of MADM mice for single-cell genetic mosaic analysis
Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., Bernthaler, T., Streicher, C., Heger, A., Johnson, R. L., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109274 · Cited by 71 · see citing works
Maintaining and Monitoring the Defined Microbiota Status of Gnotobiotic Rodents
Nicklas, W., Keubler, L. M., & Bleich, A. (2015) · ILAR Journal · doi:10.1093/ilar/ilv029 · Cited by 66 · see citing works
Intestinal Preparation Techniques for Histological Analysis in the Mouse
Williams, J. M., Duckworth, C. A., Vowell, K., et al. (2016) · Current Protocols in Mouse Biology · doi:10.1002/cpmo.2 · Cited by 67 · see citing works
Sensitivity to oxazolone induced dermatitis is transferable with gut microbiota in mice
Zachariassen, L. F., Krych, Ł., Engkilde, K., Nielsen, D. S., Kot, W., Hansen, C. H. F., & Hansen, A. K. (2017) · Scientific Reports · doi:10.1038/srep44385 · Cited by 66 · see citing works
Rodentibacter gen. nov. including Rodentibacter pneumotropicus comb. nov., Rodentibacter heylii sp. nov., Rodentibacter myodis sp. nov., Rodentibacter ratti sp. nov., Rodentibacter heidelbergensis sp. nov., Rodentibacter trehalosifermentans sp. nov., Rodentibacter rarus sp. nov., Rodentibacter mrazii and two genomospecies
Adhikary, S., Nicklas, W., Bisgaard, M., et al. (2017) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/ijsem.0.001866 · Cited by 64 · see citing works
Establishment and Characterization of Mild Atopic Dermatitis in the DNCB-Induced Mouse Model
Riedl, R., Kühn, A., Rietz, D., Hebecker, B., Glowalla, K.-G., Peltner, L. K., Jordan, P. M., Werz, O., Stefan Lorkowski, A., Wiegand, C., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512325 · Cited by 65 · see citing works
Mouse Models of Autoimmune Diabetes: The Nonobese Diabetic (NOD) Mouse
Chen, D., Thayer, T. C., Li, W., & Wong, F. S. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0385-7_6 · Cited by 62 · see citing works
Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin
Mirastschijski, U., Lupše, B., Maedler, K., Sarma, B., Radtke, A., Belge, G., Dorsch, M. M., Wedekind, D., McCawley, L. J., Boehm, G., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205234 · Cited by 62 · see citing works
“The microbiological status was examined as recommended by FELASA (Federation of European Laboratory Animal Science Associations) and the absence of listed microorganisms was confirmed [45].”
Method
Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis
Vacca, M., Leslie, J., Virtue, S., Lam, B. Y. H., Govaere, O., Tiniakos, D., Snow, S., Davies, S., Petkevicius, K., Tong, Z., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0214-9 · Cited by 60 · see citing works
A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes
Darnaud, M., Vadder, F. D., Bogeat, P., Boucinha, L., Bulteau, A., Bunescu, A., Couturier, C., Delgado, A., Dugua, H., Elie, C., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26963-9 · Cited by 54 · see citing works
Human microbiota-transplanted C57BL/6 mice and offspring display reduced establishment of key bacteria and reduced immune stimulation compared to mouse microbiota-transplantation
Lundberg, R., Toft, M., Metzdorff, S. B., Hansen, C. H. F., Licht, T. R., Bahl, M. I., & Hansen, A. K. (2020) · Scientific Reports · doi:10.1038/s41598-020-64703-z · Cited by 57 · see citing works
Myocardial Milieu Favors Local Differentiation of Regulatory T Cells
Delgobo, M., Weiß, E., Ashour, D., Richter, L., Popiolkowski, L., Arampatzi, P., Stangl, V., Arias-Loza, P., Mariotti-Ferrandiz, E., Rainer, P. P., et al. (2023) · Circulation Research · doi:10.1161/circresaha.122.322183 · Cited by 57 · see citing works
Role of endothelial nitric oxide synthase for early brain injury after subarachnoid hemorrhage in mice
Lenz, I. J., Plesnila, N., & Terpolilli, N. A. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20973787 · Cited by 53 · see citing works
Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression
Azzu, V., Vacca, M., Kamzolas, I., Hall, Z., Leslie, J., Carobbio, S., Virtue, S., Davies, S. E., Lukasik, A., Dale, M., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101210 · Cited by 52 · see citing works
Delayed Demyelination and Impaired Remyelination in Aged Mice in the Cuprizone Model
Gingele, S., Henkel, F., Heckers, S., Moellenkamp, T. M., Hümmert, M. W., Skripuletz, T., Stangel, M., & Gudi, V. (2020) · Cells · doi:10.3390/cells9040945 · Cited by 53 · see citing works
“Animals underwent routine cage maintenance once a week and were microbiologically monitored according to the Federation of European Laboratory Animal Science Associations recommendations [27].”
Method
Recommendations for Health Monitoring and Reporting for Zebrafish Research Facilities
Collymore, C., Crim, M. J., & Lieggi, C. (2016) · Zebrafish · doi:10.1089/zeb.2015.1210 · Cited by 52 · see citing works
A comparison of various methods of blood sampling in mice and rats: Effects on animal welfare
Sreelatha, H. V., Hansen, A. K., Abelson, K., et al. (2017) · Laboratory Animals · doi:10.1177/0023677217741332 · Cited by 52 · see citing works
Practical solutions for including sex as a biological variable (SABV) in preclinical neuropsychopharmacological research
Dalla, C., Jarić, I., Pavlidi, P., Hodes, G. E., Kokras, N., Bespalov, A., Kas, M. J., Steckler, T., Kabbaj, M., Würbel, H., et al. (2023) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2023.110003 · Cited by 50 · see citing works
“For experiments sensitive to these effects researchers should reconsider the experimental unit (for recommendations see part 4 and (M ¨ ahler Convenor et al., 2014)).”
Background
Composition of the Intestinal Microbiota Determines the Outcome of Virus-Triggered Colitis in Mice
Bolsega, S., Basic, M., Smoczek, A., Büettner, M., Eberl, C., Ahrens, D., Odum, K. A., Stecher, B., & Bleich, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01708 · Cited by 50 · see citing works
Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a Systemic Immune Response—Note of Caution for In vivo Infection Experiments
Schulz, D., Grumann, D., Trübe, P., Pritchett‐Corning, K. R., Johnson, S., Reppschläger, K., Gumz, J., Sundaramoorthy, N., Michalik, S., Berg, S., et al. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00152 · Cited by 50 · see citing works
“…European branches of Janvier, Charles River, and Envigo do not report the S. aureus status of SPF mice as this is not recommended for immunocompetent mice in health monitoring guidelines promulgated by the Federation of Laboratory Animal Science Associations (FELASA; Mahler Convenor et al., 2014).”
BackgroundMethodInfluentialSelf-citation
How Food Affects Colonization Resistance Against Enteropathogenic Bacteria
Kreuzer, M., & Hardt, W. (2020) · Annual Review of Microbiology · doi:10.1146/annurev-micro-020420-013457 · Cited by 43 · see citing works
Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
Mittler, E., Wec, A. Z., Tynell, J., Guardado‐Calvo, P., Byström, J. W., Polanco, L. C., O’Brien, C. M., Slough, M. M., Abelson, D. M., Serris, A., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abl5399 · Cited by 46 · see citing works
Large Animal Models for Osteochondral Regeneration
Dias, I. R., Viegas, C. A., & Carvalho, P. P. (2018) · Springer eBooks · doi:10.1007/978-3-031-80976-7_20-1 · Cited by 46 · see citing works
Physiological and Pathological Impact of Blood Sampling by Retro-Bulbar Sinus Puncture and Facial Vein Phlebotomy in Laboratory Mice
Teilmann, A. C., Madsen, A. N., Holst, B., Hau, J., Rozell, B., & Abelson, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113225 · Cited by 45 · see citing works
Murine norovirus detection in the exhaust air of IVCs is more sensitive than serological analysis of soiled bedding sentinels
Zorn, J., Ritter, B., Miller, M., et al. (2016) · Laboratory Animals · doi:10.1177/0023677216661586 · Cited by 45 · see citing works
“Sentinel serology was obtained quarterly by routine health monitoring, as described above, and exhaust air particle RT–qPCR was performed at the same time points.(6) At each stage when the sentinels were taken for monitoring, prefilters had been exposed to exhaust air for 1–4 weeks.”
BackgroundMethodInfluential
Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis
Hainzl, E., Stockinger, S., Rauch, I., Heider, S., Berry, D., Lassnig, C., Schwab, C., Rosebrock, F., Milinovich, G. J., Schlederer, M., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402565 · Cited by 44 · see citing works
Using the mouse grimace scale and behaviour to assess pain in CBA mice following vasectomy
Miller, A. L., Kitson, G. L., Skalkoyannis, B., et al. (2016) · Applied Animal Behaviour Science · doi:10.1016/j.applanim.2016.05.020 · Cited by 44 · see citing works
Cesarean Section Induces Microbiota-Regulated Immune Disturbances in C57BL/6 Mice
Zachariassen, L. F., Krych, Ł., Rasmussen, S. H., Nielsen, D. S., Kot, W., Holm, T. L., Hansen, A. K., & Hansen, C. H. F. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800666 · Cited by 44 · see citing works
From the [ Pasteurella ] pneumotropica complex to Rodentibacter spp.: an update on [ Pasteurella ] pneumotropica
Benga, L., Sager, M., & Christensen, H. K. (2018) · Veterinary Microbiology · doi:10.1016/j.vetmic.2018.03.011 · Cited by 43 · see citing works
Research-Relevant Conditions and Pathology of Laboratory Mice, Rats, Gerbils, Guinea Pigs, Hamsters, Naked Mole Rats, and Rabbits
Cooper, T. K., Meyerholz, D. K., Beck, A. P., Delaney, M. A., Piersigilli, A., Southard, T. L., & Brayton, C. F. (2021) · ILAR Journal · doi:10.1093/ilar/ilab022 · Cited by 44 · see citing works
Composition of Intestinal Microbiota in Immune-Deficient Mice Kept in Three Different Housing Conditions
Thöne‐Reineke, C., Fischer, A., Friese, C., Briesemeister, D., Göbel, U. B., Kammertoens, T., Bereswill, S., & Heimesaat, M. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113406 · Cited by 42 · see citing works
New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties
Herlin, M., Finnilä, M., Zioupos, P., Aula, A. S., Risteli, J., Miettinen, H. M., Jämsä, T. J., Tuukkanen, J., Korkalainen, M., Håkansson, H., et al. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.09.002 · Cited by 42 · see citing works
Exhaust Air Dust Monitoring is Superior to Soiled Bedding Sentinels for the Detection of Pasteurella pneumotropica in Individually Ventilated Cage Systems.
Miller, M., Ritter, B., Zorn, J., et al. (2016) · PubMed · Cited by 42 · see citing works
Understanding gene functions and disease mechanisms: Phenotyping pipelines in the German Mouse Clinic
Fuchs, H., Aguilar‐Pimentel, J. A., Amarie, O. V., Becker, L., Calzada‐Wack, J., Cho, Y.-L., Garrett, L., Hölter, S. M., Irmler, M., Kistler, M., et al. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.09.048 · Cited by 42 · see citing works
Environmental samples make soiled bedding sentinels dispensable for hygienic monitoring of IVC-reared mouse colonies
Miller, M., & Brielmeier, M. (2017) · Laboratory Animals · doi:10.1177/0023677217739329 · Cited by 42 · see citing works
Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis
Borisova, M. A., Snytnikova, O. A., Litvinova, E. A., Achasova, K. M., Babochkina, T. I., Pindyurin, A. V., Tsentalovich, Y. P., & Kozhevnikova, E. N. (2020) · Nutrients · doi:10.3390/nu12020445 · Cited by 41 · see citing works
“All animals used had specific pathogen free (SPF) status, which was tested quarterly according to Federation of European Laboratory Animal Science Associations (FELASA) recommendations [25].”
Method
Notch Signaling in the Dynamics of Perivascular Stem Cells and their Niches
Pagella, P., Roditi, L. D. V., Stadlinger, B., Moor, A. E., & Mitsiadis, T. A. (2021) · Stem Cells Translational Medicine · doi:10.1002/sctm.21-0086 · Cited by 41 · see citing works
“The mice were free of all viral, bacterial, and parasitic pathogens listed in FELASA recommendations.(38) To generate Notch3 R26 mice, we crossed R26 (Gt(ROSA)26Sor; Jax: 007576) mice with Notch3 (Notch3; MGI: 5304914) mice.”
Background
Osteogenic efficacy of strontium hydroxyapatite micro-granules in osteoporotic rat model
Chandran, S., Suresh Babu, S., Sreelatha, H. V., et al. (2016) · Journal of Biomaterials Applications · doi:10.1177/0885328216647197 · Cited by 40 · see citing works
Effect of three different forms of handling on the variation of aggression-associated parameters in individually and group-housed male C57BL/6NCrl mice
Mertens, S., Vogt, M. A., Gass, P., Palme, R., Hiebl, B., & Chourbaji, S. (2019) · PLoS ONE · doi:10.1371/journal.pone.0215367 · Cited by 40 · see citing works
Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution
Buchheister, S., & Bleich, A. (2021) · Animals · doi:10.3390/ani11051410 · Cited by 42 · see citing works
“Those recommendations are regularly updated and available for different species, including rodents, guinea pigs and rabbits [17], ruminants and pigs [141] and non-human primates [142].”
Background
Reference genes for valid gene expression studies on rat dental, periodontal and alveolar bone tissue by means of RT-qPCR with a focus on orthodontic tooth movement and periodontitis
Kirschneck, C., Proff, P., Fanghänel, J., Wolf, M. F., Roldán, J. C., & Römer, P. (2015) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2015.11.005 · Cited by 39 · see citing works
“Health monitoring (serologic and microbiological testing) was performed according to FELASA guidelines once per year (stock sentinels) (Mähler Convenor et al., 2014).”
Method
Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex
Laukoter, S., Pauler, F. M., Beattie, R., Amberg, N., Hansen, A. H., Streicher, C., Penz, T., Bock, C., & Hippenmeyer, S. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.031 · Cited by 36 · see citing works
Human CD34 + Hematopoietic Stem Cell–Engrafted NSG Mice: Morphological and Immunophenotypic Features
Blümich, S., Zdimerova, H., Münz, C., Kipar, A., & Pellegrini, G. (2020) · Veterinary Pathology · doi:10.1177/0300985820948822 · Cited by 39 · see citing works
Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice
Rasmussen, T. S., Mentzel, C. M. J., Danielsen, M. R., Jakobsen, R. R., Zachariassen, L. F., Castro-Mejía, J. L., Brunse, A., Hansen, L. H., Hansen, C. H. F., Hansen, A. K., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2208504 · Cited by 38 · see citing works
The Mammalian Microbiome and Its Importance in Laboratory Animal Research
Bleich, A., & Fox, J. G. (2015) · ILAR Journal · doi:10.1093/ilar/ilv031 · Cited by 38 · see citing works
Injection anaesthesia with fentanyl–midazolam–medetomidine in adult female mice: importance of antagonization and perioperative care
Fleischmann, T., Jirkof, P., Henke, J., et al. (2016) · Laboratory Animals · doi:10.1177/0023677216631458 · Cited by 37 · see citing works
Standardization in host–microbiota interaction studies: challenges, gnotobiology as a tool, and perspective
Mooser, C., de Agüero, M. G., & Ganal-Vonarburg, S. C. (2018) · Current Opinion in Microbiology · doi:10.1016/j.mib.2018.07.007 · Cited by 36 · see citing works
Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge
Zheng, X., Oduro, J. D., Boehme, J. D., Borkner, L., Ebensen, T., Heise, U., Gereke, M., Pils, M. C., Krmpotić, A., Guzmán, C. A., et al. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1008036 · Cited by 37 · see citing works
Major oscillations in spontaneous home-cage activity in C57BL/6 mice housed under constant conditions
Pernold, K., Rullman, E., & Ulfhake, B. (2021) · Scientific Reports · doi:10.1038/s41598-021-84141-9 · Cited by 38 · see citing works
Seoul Virus Infection in Humans, France, 2014–2016
Reynes, J., Carli, D., Bour, J., et al. (2017) · Emerging infectious diseases · doi:10.3201/eid2306.160927 · Cited by 36 · see citing works
16S ribosomal DNA sequence-based identification of bacteria in laboratory rodents: a practical approach in laboratory animal bacteriology diagnostics
Benga, L., Benten, W. P. M., Engelhardt, E., et al. (2014) · Laboratory Animals · doi:10.1177/0023677214538240 · Cited by 35 · see citing works
“Materials and methods Bacterial isolates and conventional identification methods The bacterial strains included in this study (Table 1) were isolated during the routine microbiological monitoring program of the mouse and rat colonies from the Animal Research Facility of Heinrich Heine University Düsseldorf, which is b…”
Method
Age-related decline in the resistance of mice to bacterial infection and in LPS/TLR4 pathway-dependent neutrophil responses
Hornigold, K., Chu, J. Y., Chetwynd, S. A., Machin, P. A., Crossland, L., Pantarelli, C., Anderson, K. E., Hawkins, P. T., Segonds-Pichon, A., Oxley, D., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.888415 · Cited by 35 · see citing works
Time to Integrate to Nest Test Evaluation in a Mouse DSS-Colitis Model
Häger, C., Keubler, L. M., Biernot, S., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0143824 · Cited by 34 · see citing works
“Routine microbiologic monitoring according to recommendations of the Federation of European Laboratory Animal Science Associations did not reveal any evidence of infection with common murine pathogens [18, 19].”
Method
Efficacy of Soiled Bedding Transfer for Transmission of Mouse and Rat Infections to Sentinels: A Systematic Review
Bruin, W. C. C. D., van de Ven, E. M. E., & Hooijmans, C. R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158410 · Cited by 34 · see citing works
RETRACTED: Modeling Cardiac Dysfunction Following Traumatic Hemorrhage Injury: Impact on Myocardial Integrity
Wall, J., Naganathar, S., Praditsuktavorn, B., Bugg, O. F., McArthur, S., Thiemermann, C., Tremoleda, J. L., & Brohi, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02774 · Cited by 34 · see citing works
Retracted
B cell‐intrinsic changes with age do not impact antibody‐secreting cell formation but delay B cell participation in the germinal centre reaction
Lee, J. L., Fra-Bidó, S., Burton, A. R., Innocentin, S., Hill, D. L., & Linterman, M. A. (2022) · Aging Cell · doi:10.1111/acel.13692 · Cited by 34 · see citing works
Colitis-associated intestinal microbiota regulates brain glycine and host behavior in mice
Morozova, M. V., Borisova, M. A., Snytnikova, O. A., Achasova, K. M., Litvinova, E. A., Tsentalovich, Y. P., & Kozhevnikova, E. N. (2022) · Scientific Reports · doi:10.1038/s41598-022-19219-z · Cited by 35 · see citing works
“All animals had SPF status, which was tested quarterly according to Federation of European laboratory animal science association’s (FELASA) recommendations (Mähler et al., 2014).”
Method
The direct oral anticoagulants rivaroxaban and dabigatran do not inhibit orthotopic growth and metastasis of human breast cancer in mice
Buijs, J. T., Laghmani, E. H., van den Akker, R. F. P., Tieken, C., Vletter, E. M., van der Molen, K., Crooijmans, J. J., Kroone, C., Dévédec, S. E. L., van der Pluijm, G., et al. (2019) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14443 · Cited by 32 · see citing works
Severity assessment in mice subjected to carbon tetrachloride
Ernst, L., Zieglowski, L., Schulz, M., Moss, M., Meyer, M., Weiskirchen, R., Palme, R., Hamann, M., Talbot, S. R., & Tolba, R. H. (2020) · Scientific Reports · doi:10.1038/s41598-020-72801-1 · Cited by 32 · see citing works
Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ
Webb, L. M. C., Fra-Bidó, S., Innocentin, S., Matheson, L. S., Attaf, N., Bignon, A., Novarino, J., Fazilleau, N., & Linterman, M. A. (2021) · Aging Cell · doi:10.1111/acel.13295 · Cited by 33 · see citing works
“No primary pathogens or additional agents listed in the FELASA recommendations (Mahler et al., 2014) were detected during health monitoring surveys of the stock holding rooms.”
Background
Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A
Panova, E. A., Kleymenov, D. A., Shcheblyakov, D. V., Bykonia, E. N., Mazunina, E. P., Dzharullaeva, A. S., Zolotar, A. N., Derkaev, A. A., Esmagambetov, I. B., Sorokin, I. I., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1098302 · Cited by 34 · see citing works
T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors
Middelburg, J., Sluijter, M., Schaap, G., Göynük, B., Lloyd, K. A., Ovcinnikovs, V., Zom, G. G., Marijnissen, R. J., Groeneveldt, C., Griffioen, L., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44308-6 · Cited by 32 · see citing works
“The health status of the animals was monitored over time and all animals were tested negative for agents listed in the FELASA (Federation of European Laboratory Animal Science Associations) guidelines for speci ﬁ c-pathogen free mouse colonies 55 .”
Participation of the spleen in the IgA immune response in the gut
Weiberg, D., Basic, M., Smoczek, M., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0205247 · Cited by 32 · see citing works
Dietary prebiotics promote intestinal Prevotella in association with a low-responding phenotype in a murine oxazolone-induced model of atopic dermatitis
Laigaard, A., Krych, Ł., Zachariassen, L. F., Ellegaard‐Jensen, L., Nielsen, D. S., Hansen, A. K., & Hansen, C. H. F. (2020) · Scientific Reports · doi:10.1038/s41598-020-78404-0 · Cited by 32 · see citing works
A new CUT&RUN low volume-urea (LoV-U) protocol optimized for transcriptional co-factors uncovers Wnt/β-catenin tissue-specific genomic targets
Zambanini, G., Nordin, A., Jonasson, M. E., Pagella, P., & Cantù, C. (2022) · Development · doi:10.1242/dev.201124 · Cited by 28 · see citing works
“The mice were free of all viral, bacterial and parasitic pathogens listed in FELASA recommendations (Mähler et al., 2014).”
Background
Wheel running behaviour in group-housed female mice indicates disturbed wellbeing due to DSS colitis
Weegh, N., Füner, J., Janke, O., Winter, Y., Jung, C., Struve, B., Wassermann, L., Lewejohann, L., Bleich, A., & Häger, C. (2019) · Laboratory Animals · doi:10.1177/0023677219879455 · Cited by 31 · see citing works
“Routine health surveillance and microbiologic monitoring according to the Federation of European Laboratory Animal Associations recommendations did not reveal any evidence of infection with common murine pathogens.(13) Mice were maintained in a room with controlled environment (21–23 C; relative humidity 55 5%; 14/10…”
PCR and RT-PCR in the Diagnosis of Laboratory Animal Infections and in Health Monitoring
Compton, S. R. (2020) · Journal of the American Association for Laboratory Animal Science · doi:10.30802/aalas-jaalas-20-000008 · Cited by 31 · see citing works
Reliability of the Mouse Grimace Scale in C57BL/6JRj Mice
Hohlbaum, K., Corte, G. M., Humpenöder, M., et al. (2020) · Animals · doi:10.3390/ani10091648 · Cited by 31 · see citing works
Lidocaine and bupivacaine as part of multimodal pain management in a C57BL/6J laparotomy mouse model
Durst, M. S., Arras, M., Palme, R., Talbot, S. R., & Jirkof, P. (2021) · Scientific Reports · doi:10.1038/s41598-021-90331-2 · Cited by 32 · see citing works
AALAS/FELASA Working Group on Health Monitoring of rodents for animal transfer.
Pritchett‐Corning, K. R., Prins, J., Feinstein, R. E., et al. (2014) · PubMed · Cited by 31 · see citing works
Self-citation
Characterization of Different Inflammatory Skin Conditions in a Mouse Model of DNCB-Induced Atopic Dermatitis
Riedl, R., Kühn, A., Hupfer, Y., Hebecker, B., Peltner, L. K., Jordan, P. M., Werz, O., Stefan Lorkowski, A., Wiegand, C., & Wallert, M. (2023) · Inflammation · doi:10.1007/s10753-023-01943-x · Cited by 30 · see citing works
High-Resolution Melting Curve Analysis for Identification of Pasteurellaceae Species in Experimental Animal Facilities
Miller, M., Zorn, J., & Brielmeier, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142560 · Cited by 29 · see citing works
“pneumotropica is currently recommended [5].”
Genetic restriction of antigen-presentation dictates allergic sensitization and disease in humanized mice
Neunkirchner, A., Kratzer, B., Köhler, C., Smole, U., Mager, L. F., Schmetterer, K. G., Trapin, D., Reichl, V., Rosloniec, E. F., Naumann, R., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.04.001 · Cited by 29 · see citing works
“Sentinel mice were screened for and found to be free ofmouse pathogenic viruses, bacteria and parasites according to FELASA 2014 recommendations (Mahler Convenor et al., 2014).”
Method
Laboratory diagnostics of murine blood for detection of mouse cytomegalovirus (MCMV)-induced hepatitis
Stahl, F. R., Jung, R., Jazbutyte, V., Ostermann, E., Tödter, S., Brixel, R., Kemmer, A., Halle, S., Rose‐John, S., Messerle, M., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-33167-7 · Cited by 29 · see citing works
Lifetime Dependent Variation of Stress Hormone Metabolites in Feces of Two Laboratory Mouse Strains
Kolbe, T., Palme, R., Tichy, A., & Rülicke, T. (2015) · PLoS ONE · doi:10.1371/journal.pone.0136112 · Cited by 29 · see citing works
“SPF quality of the animals was confirmed by a sentinel program according to FELASA recommendations [25].”
Method
Healing of fractures in osteoporotic bones in mice treated with bisphosphonates – A transcriptome analysis
Hauser, M., Siegrist, M., Keller, I., & Hofstetter, W. (2018) · Bone · doi:10.1016/j.bone.2018.04.017 · Cited by 29 · see citing works

Cloning and Characterization of Rat BAT3 cDNA
Ozaki, T., Hanaoka, E., Naka, M., et al. (1999) · DNA and Cell Biology · doi:10.1089/104454999315222 · Cited by 22 · see citing works
EFFECT OF THE NEMATODE PHASMARHABDITIS HERMAPHRODITA ON YOUNG STAGES OF THE PEST SLUG ARION LUSITANICUS
Grimm, B. (2002) · Journal of Molluscan Studies · doi:10.1093/mollus/68.1.25 · Cited by 41 · see citing works
HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53Preprint
Sasaki, T., Gan, E. C., Wakeham, A. C., Kornbluth, S. A., Mak, T. W., & Okada, H. (2007) · Genes & Development · doi:10.1101/gad.1534107 · Cited by 127 · see citing works
The Animal Welfare Act at Fifty: Problems and Possibilities in Animal Testing Regulation
Lee, C. G. (2016) · Lincoln (University of Nebraska) · Cited by 3 · see citing works
The Animal Welfare Act as Applied to Primate Animal Laboratories
Schwindaman, D. F. (1983) · Journal of Medical Primatology · doi:10.1111/j.1600-0684.1983.tb00081.x · Cited by 1 · see citing works

Authors: FELASA working group on revision of guidelines for health monitoring of rodents and rabbits, Mähler (Convenor), M., Berard, M., Feinstein, R., Gallagher, A., Illgen-Wilcke, B., Pritchett-Corning, K., & Raspa, M.
Affiliations: GV-SOLAS, Gesellschaft für Versuchstierkunde
Swedish Veterinary Agency (SE)
Medical Research Council (GB)
University of Washington (US)
AALAS, American Association for Laboratory Animal Science
National Research Council (IT)
ORCID: Berard, M
Raspa, M
Venue: Laboratory Animals
Publisher: SAGE Publications
Published: 2014-02-04
Volume: 48
Issue: 3
Pages: 178-192
ISSN: 0023-6772 (ISSN-L)
1758-1117
DOI: 10.1177/0023677213516312
OpenAlex: W2153218957
Semantic Scholar: 3f0f57dfc81bdbf0b4adc599d3696d57bd2535a2
Cited by: 646
References: 382
Citations by year: 2026: 36 · 2025: 63 · 2024: 69 · 2023: 60 · 2022: 67 · 2021: 73 · 2020: 62 · 2019: 62 · 2018: 47 · 2017: 42 · 2016: 28 · 2015: 24 · 2014: 12 · 2013: 1
FWCI: 51.91
Type: journal article
Language: en
Update notices: correction (2014-09-02)
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Laboratory Animals (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
Health Sciences › Veterinary › Small Animals › Animal Behavior and Welfare Studies
Keywords: laboratory animal health monitoring, sentinel animals, opportunistic pathogens, laboratory mice, laboratory rats, golden hamster, guinea pig, rabbits, laboratory animal medicine

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FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units

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