A mutation in Tmem135 causes progressive sensorineural hearing loss

Area of Science:

• Genetics
• Otolaryngology
• Cell Biology

Background:

• Transmembrane protein 135 (TMEM135) is a conserved protein involved in mitochondrial and peroxisomal functions.
• Previous research links TMEM135 to metabolic processes, but its role in the auditory system is unexplored.

Purpose of the Study:

• To investigate the function of TMEM135 in the mammalian auditory system.
• To determine the impact of Tmem135 mutations on hearing and cochlear structure.

Main Methods:

• Utilized wild-type and Tmem135 mutant (FUN025) mice on a CBA/CaJ background.
• Assessed auditory function using auditory brainstem response (ABR) testing at various frequencies and ages.
• Examined cochlear histology, including hair cell survival, spiral ganglion neuron density, and stria vascularis integrity.
• Analyzed TMEM135 expression patterns via BaseScope RNA in situ hybridization.
• Investigated TMEM135 colocalization with mitochondria in hair cells using Volocity and Costes analysis.

Main Results:

• Tmem135 FUN025 mutant mice developed progressive sensorineural hearing loss starting by 3 months and becoming profound by 12 months.
• Significant loss of outer hair cells and moderate changes in inner hair cells, spiral ganglion neurons, and stria vascularis were observed in mutant mice.
• TMEM135 expression was detected in key cochlear cell types: inner hair cells, outer hair cells, supporting cells, and stria vascularis.
• TMEM135 was found to colocalize with mitochondria within hair cells.

Conclusions:

• The FUN025 mutation in Tmem135 leads to age-dependent progressive hearing impairment.
• TMEM135 plays a critical role in the survival and function of cochlear cells, particularly hair cells.
• TMEM135 is essential for maintaining auditory sensory function throughout the aging process.