Synaptojanin2 Mutation Causes Progressive High-frequency Hearing Loss in Mice.

Area of Science:

• Neuroscience
• Genetics
• Otolaryngology

Background:

• Progressive hearing loss is common, yet its molecular basis remains unclear.
• Synaptojanin2 (Synj2), a phosphatidylinositol phosphatase involved in endocytosis, has been implicated in age-related hearing decline.

Purpose of the Study:

• To investigate the role of Synj2 in progressive hearing loss by examining vesicle trafficking in sensory hair cell synapses.
• To determine if Synj2 mutations affect hair cell function and contribute to hearing impairment.

Main Methods:

• Studied a novel mouse mutation in Synj2 (Synj2tm1b).
• Assessed auditory function using auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE).
• Examined hair cell structure and synaptic function via microscopy and electrophysiology.

Main Results:

• Mice showed declining auditory thresholds starting at 3-4 weeks.
• Outer hair cell (OHC) stereocilia fusion and degeneration were observed, primarily in the basal turn.
• No defects in inner hair cell (IHC) exocytosis/endocytosis or synaptic abnormalities were found; endocochlear potentials (EP) were normal.

Conclusions:

• Synj2 is essential for maintaining hearing but not for its initial development.
• The progressive hearing loss in Synj2 mutants appears to originate from OHC degeneration, despite the precise mechanism remaining elusive.