{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:44:56Z","timestamp":1785433496114,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds National de la Recherche Scientifique","doi-asserted-by":"publisher","award":["J.0193.26"],"award-info":[{"award-number":["J.0193.26"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds National de la Recherche Scientifique","doi-asserted-by":"publisher","award":["1S00526F"],"award-info":[{"award-number":["1S00526F"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"award":["J.0193.26"],"award-info":[{"award-number":["J.0193.26"]}],"id":[{"id":"https:\/\/ror.org\/03q83t159","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1S00526F"],"award-info":[{"award-number":["1S00526F"]}],"id":[{"id":"https:\/\/ror.org\/03q83t159","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"FRIA","doi-asserted-by":"publisher","award":["FC 49797"],"award-info":[{"award-number":["FC 49797"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"post-doctoral FNRS CCL","doi-asserted-by":"publisher","award":["FC 29281"],"award-info":[{"award-number":["FC 29281"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Eosinophilic chronic rhinosinusitis (eCRS) is an upper respiratory condition frequently associated with olfactory dysfunction (OD). Despite its high prevalence, the mechanisms underlying OD remain poorly understood. Several eCRS models have been described, but their olfactory phenotypes are poorly characterized. In this study, we compared two of the most frequently used mouse models of eCRS in order to standardize in vivo research on eCRS-related OD. Male and female mice were challenged with ovalbumin (OVA) combined with Staphylococcus aureus enterotoxin B (SEB) over a 13-week protocol or with OVA combined with Aspergillus oryzae protease (AP) for 6 or 12 weeks. Olfactory function was assessed using the buried food test and habituation\/dishabituation test. After sacrifice, the integrity and inflammation of the olfactory epithelium were assessed on coronal skull sections by (immuno)histology, including sex as a biological variable. Both models exhibited impaired olfactory function, reduced olfactory epithelium surface area and thickness, and eosinophil infiltration of the olfactory mucosa. The OVA-AP model showed additional presence of neutrophils in the olfactory mucosa, suggesting a mixed inflammatory response. No functional or histological difference was detected between male and female mice, except for epithelial thickness in OVA-SEB control mice. Overall, both murine models are suitable for mechanistic studies of OD in eCRS, with the AP-12-week model displaying the most pronounced inflammation.<\/jats:p>","DOI":"10.3390\/cells15121118","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:49:55Z","timestamp":1782121795000},"page":"1118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Characterization of Olfactory Dysfunction in Mouse Models of Eosinophilic Chronic Rhinosinusitis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1878-1027","authenticated-orcid":false,"given":"Agn\u00e8s","family":"Dekeyser","sequence":"first","affiliation":[{"name":"Pole of Lung, Nose and Skin Research (LUNS), Institute of Experimental and Clinical Research (IREC), UCLouvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryl\u00e8ne","family":"Lecocq","sequence":"additional","affiliation":[{"name":"Pole of Lung, Nose and Skin Research (LUNS), Institute of Experimental and Clinical Research (IREC), UCLouvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Camboni","sequence":"additional","affiliation":[{"name":"Laboratory of Gynecology, Institute of Experimental and Clinical Research (IREC), UCLouvain, 1200 Brussels, Belgium"},{"name":"Department of Pathology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Gohy","sequence":"additional","affiliation":[{"name":"Pole of Lung, Nose and Skin Research (LUNS), Institute of Experimental and Clinical Research (IREC), UCLouvain, 1200 Brussels, Belgium"},{"name":"Department of Pulmonology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Pilette","sequence":"additional","affiliation":[{"name":"Pole of Lung, Nose and Skin Research (LUNS), Institute of Experimental and Clinical Research (IREC), UCLouvain, 1200 Brussels, Belgium"},{"name":"Department of Pulmonology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8851-3534","authenticated-orcid":false,"given":"Brian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Developmental, Molecular and Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Huart","sequence":"additional","affiliation":[{"name":"Institute of Neurosciences, UCLouvain, 1200 Brussels, Belgium"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Hox","sequence":"additional","affiliation":[{"name":"Pole of Lung, Nose and Skin Research (LUNS), Institute of Experimental and Clinical Research (IREC), UCLouvain, 1200 Brussels, Belgium"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00441-020-03367-7","article-title":"The importance of the olfactory system in human well-being, through nutrition and social behavior","volume":"383","author":"Boesveldt","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin22.483","article-title":"Position paper on olfactory dysfunction: 2023","volume":"61","author":"Whitcroft","year":"2023","journal-title":"Rhinol. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00106-019-0614-x","article-title":"Diagnostik und Therapie von Riechst\u00f6rungen","volume":"67","author":"Damm","year":"2019","journal-title":"HNO"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1398-9995.2011.02646.x","article-title":"Chronic rhinosinusitis in Europe\u2013an underestimated disease. A GA2LEN study","volume":"66","author":"Hastan","year":"2011","journal-title":"Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dekeyser, A., Huart, C., Hummel, T., and Hox, V. (2024). Olfactory Loss in Rhinosinusitis: Mechanisms of Loss and Recovery. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084460"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/s41590-022-01312-0","article-title":"Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis","volume":"23","author":"Wang","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"349","DOI":"10.21053\/ceo.2025-00003","article-title":"Functional and Morphological Changes in the Olfactory Epithelium of Mouse Models With Upper Respiratory Inflammation and Olfactory Dysfunction","volume":"18","author":"Yoo","year":"2025","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_9","first-page":"353","article-title":"Mouse model of Staphylococcus aureus- and Pseudomonas aeruginosa-induced neutrophilic chronic rhinosinusitis","volume":"63","author":"Lecocq","year":"2025","journal-title":"Rhinol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102453","DOI":"10.1016\/j.nano.2021.102453","article-title":"Vascular permeability in chronic rhinosinusitis enhances accumulation and retention of nanoscale pegylated liposomes","volume":"38","author":"Khurana","year":"2021","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sun, H., Damania, A., Mair, M.L., Otukoya, E., Li, Y.-D., Polsky, K., Zeng, Y., Alt, J.A., Citardi, M.J., and Corry, D.B. (2022). STAT6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis and Asthma, A Model of Unified Airway Disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.818017"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/alr.22053","article-title":"Olfactory loss in chronic rhinosinusitis is associated with neuronal activation of c-Jun N-terminal kinase","volume":"8","author":"Victores","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_13","first-page":"14","article-title":"Validation and shortcomings of the most common mouse model of chronic rhinosinusitis with nasal polyps","volume":"62","author":"Lecocq","year":"2024","journal-title":"Rhinol. J."},{"key":"ref_14","unstructured":"Maloy, S., and Hughes, K. (2013). BALB\/c Mouse. Brenner\u2019s Encyclopedia of Genetics, Academic Press. [2nd ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"396","DOI":"10.21053\/ceo.2019.01837","article-title":"Strain-Specific Differences in House Dust Mite (Dermatophagoides farinae)-Induced Mouse Models of Allergic Rhinitis","volume":"13","author":"Lee","year":"2020","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jaci.2024.02.021","article-title":"Murine model of eosinophilic chronic rhinosinusitis with nasal polyposis inducing neuroinflammation and olfactory dysfunction","volume":"154","author":"Huang","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0006-8993(02)02566-0","article-title":"Impaired olfactory behavior in mice deficient in the alpha subunit of G(o)","volume":"941","author":"Luo","year":"2002","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.neuron.2014.06.015","article-title":"Endothelial NT-3 Delivered by Vasculature and CSF Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction","volume":"83","author":"Delgado","year":"2014","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sorokowski, P., Karwowski, M., Misiak, M., Marczak, M.K., Dziekan, M., Hummel, T., and Sorokowska, A. (2019). Sex Differences in Human Olfaction: A Meta-Analysis. Front. Psychol., 10.","DOI":"10.3389\/fpsyg.2019.00242"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e013246","DOI":"10.1136\/bmjopen-2016-013246","article-title":"Prevalence and risk factors of taste and smell impairment in a nationwide representative sample of the US population: A cross-sectional study","volume":"6","author":"Liu","year":"2016","journal-title":"BMJ Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3899","DOI":"10.1007\/s00405-017-4717-2","article-title":"Development of a mouse model of eosinophilic chronic rhinosinusitis with nasal polyp by nasal instillation of an Aspergillus protease and ovalbumin","volume":"274","author":"Kim","year":"2017","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.2500\/ajra.2011.25.3727","article-title":"Staphylococcus aureus Enterotoxin B Contributes to Induction of Nasal Polypoid Lesions in an Allergic Rhinosinusitis Murine Model","volume":"25","author":"Kim","year":"2011","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Krakauer, T. (2019). Staphylococcal Superantigens: Pyrogenic Toxins Induce Toxic Shock. Toxins, 11.","DOI":"10.3390\/toxins11030178"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/cea.13760","article-title":"Staphylococcus aureus enterotoxin B disrupts nasal epithelial barrier integrity","volume":"51","author":"Martens","year":"2020","journal-title":"Clin. Exp. Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2015.12.1324","article-title":"Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers","volume":"137","author":"Tomassen","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/lary.26229","article-title":"Patterns of olfactory impairment reflect underlying disease etiology","volume":"127","author":"Whitcroft","year":"2016","journal-title":"Laryngoscope"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1152\/jn.90479.2008","article-title":"Neurobiology of a Simple Memory","volume":"100","author":"Wilson","year":"2008","journal-title":"J. Neurophysiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/01926233241252114","article-title":"Histology Atlas of the Developing Mouse Respiratory System From Prenatal Day 9.0 Through Postnatal Day 30","volume":"52","author":"Parslow","year":"2024","journal-title":"Toxicol. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1111\/all.16582","article-title":"Amphiregulin Mediates Epithelial Cell\u2013Eosinophil Interactions and Amplifies Inflammation in Chronic Rhinosinusitis With Nasal Polyps","volume":"80","author":"Zhao","year":"2025","journal-title":"Allergy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4168\/aair.2025.17.1.77","article-title":"Inotodiol Attenuates Mucosal Inflammation in a Mouse Model of Eosinophilic Chronic Rhinosinusitis","volume":"17","author":"Chung","year":"2025","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"994","DOI":"10.4168\/aair.2020.12.6.994","article-title":"Chloroquine Treatment Suppresses Mucosal Inflammation in a Mouse Model of Eosinophilic Chronic Rhinosinusitis","volume":"12","author":"Choi","year":"2020","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1002\/lary.22190","article-title":"The role of TNF-\u03b1 in inflammatory olfactory loss","volume":"121","author":"Sultan","year":"2011","journal-title":"Laryngoscope"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1523\/JNEUROSCI.4507-09.2010","article-title":"A Genetic Model of Chronic Rhinosinusitis-Associated Olfactory Inflammation Reveals Reversible Functional Impairment and Dramatic Neuroepithelial Reorganization","volume":"30","author":"Lane","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.otohns.2010.08.016","article-title":"Relationship between olfactory function and olfactory neuronal population in C57BL6 mice injected intraperitoneally with 3-methylindole","volume":"143","author":"Kim","year":"2010","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.bbrc.2019.03.110","article-title":"Construction of an irreversible allergic rhinitis-induced olfactory loss mouse model","volume":"513","author":"Liang","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.bbi.2025.05.001","article-title":"A long-term mixed eosinophilic and neutrophilic chronic rhinosinusitis C57BL\/6 mouse model with neuroinflammation, olfactory dysfunction and anxiety-like behaviors","volume":"128","author":"Zhang","year":"2025","journal-title":"Brain Behav. Immun."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/12\/1118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:05:36Z","timestamp":1782122736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/12\/1118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,20]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cells15121118"],"URL":"https:\/\/doi.org\/10.3390\/cells15121118","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,20]]}}}