Comparative Characterization of Olfactory Dysfunction in Mouse Models of Eosinophilic Chronic Rhinosinusitis

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.