King's College London

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.