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

TY - JOUR

T1 - The Effect of a Pex3 Mutation on Hearing and Lipid Content of the Inner Ear

AU - Kochaj, Rafael M.

AU - Martelletti, Elisa

AU - Ingham, Neil J.

AU - Buniello, Annalisa

AU - Sousa, Bebiana C.

AU - Wakelam, Michael J.O.

AU - Lopez-Clavijo, Andrea F.

AU - Steel, Karen P.

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/10

Y1 - 2022/10

N2 - 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.

AB - 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.

KW - hearing loss

KW - lipidomics

KW - mouse mutant

KW - peroxisome disorders

KW - synaptic defect

UR - http://www.scopus.com/inward/record.url?scp=85140644058&partnerID=8YFLogxK

U2 - 10.3390/cells11203206

DO - 10.3390/cells11203206

M3 - Article

C2 - 36291074

AN - SCOPUS:85140644058

SN - 2073-4409

VL - 11

JO - Cells

JF - Cells

IS - 20

M1 - 3206

ER -