The Effect of a Pex3 Mutation on Hearing and Lipid Content of the Inner Ear

Peroxisome biogenesis disorders (due to PEX gene mutations) are associated with symptoms
that range in severity and can lead to early childhood death, but a common feature is hearing
impairment. In this study, mice carrying Pex3 mutations were found to show normal auditory development
followed by an early-onset progressive increase in auditory response thresholds. The only
structural defect detected in the cochlea at four weeks old was the disruption of synapses below inner
hair cells. A conditional approach was used to establish that Pex3 expression is required locally within
the cochlea for normal hearing, rather than hearing loss being due to systemic effects. A lipidomics
analysis of the inner ear revealed a local reduction in plasmalogens in the Pex3 mouse mutants,
comparable to the systemic plasmalogen reduction reported in human peroxisome biogenesis disorders.
Thus, mice with Pex3 mutations may be a useful tool to understand the physiological basis of
peroxisome biogenesis disorders.