<p><b>OBJECTIVE</b>To observe the alterations of the auditory function and morphology of the ear in the mouse sialidosis models which has been generated by targeted deletion of lysosomal neuraminidase gene (Neul) and closely resembled the phenotypes in corresponding human conditions, and to explore pathophysiological mechanisms of hearing impairment.</p><p><b>METHODS</b>Neul homozygous (Neul -/-) mice at 3 weeks, 2 and 4 months of age, and their wildtype littermates (Neu1 +/+) were examined for auditory thresholds through auditory brainstem responses (ABR) to click, 8, 16, and 32 kHz stimuli. Morphological analyses in ears were performed by series temporal bone section and light microscopy.</p><p><b>RESULTS</b>Neul -/- mice at 3 weeks of age showed an elevated ABR threshold, 50-55 dB above those of Neul +/+ mice. Up to 2 and 4 months of age, their thresholds were further elevated for 60-68 dB. There were distinct pathological changes of middle and inner ear of 3 weeks of age in Neul -/- mice, especially at 2-4 months of age there were significant cerumen occlusion in the external auditory canal and severe otitis media. Vacuolation associated with lysosomal storage was observed within ossicles and cochlear bone cells, stria vascularis cells, spiral ganglion neurons and macrophages, spiral limbus, spiral prominence, Reissner's membrane cells, and the mesothelial cells of the perilymphatic scala and basilar membrane, but not within the organ of Corti. Vestibular ganglion neurons, hair cells and supporting cells in cristae and maculae also showed vacuolation.</p><p><b>CONCLUSIONS</b>The deficiency of lysosomal neuraminidase may result in a serious hearing loss and morphological alterations of ear. The external auditory canal obstruction, otitis media and ossicle changes may cause conductive hearing loss, and the defects in lysosomal storage of neurons, stria vascularis, spiral limbus, Reissner's membrane and basilar membrane cells may contribute to sensorineural deafness.</p>