Progressive deafness and altered cochlear innervation in knock-out mice lacking prosaposin

Area of Science:

• Neuroscience
• Otolaryngology
• Developmental Biology

Background:

• Prosaposin was identified as a potential interacting protein with the nicotinic acetylcholine receptor (nAChR) alpha10 subunit.
• The developmental expression of prosaposin in the rodent inner ear was not previously well-characterized.

Purpose of the Study:

• To characterize the expression pattern of prosaposin in the developing rodent inner ear.
• To investigate the role of prosaposin in hearing and inner ear development using a knockout mouse model.

Main Methods:

• Yeast two-hybrid screening to identify interacting proteins.
• Immunohistochemistry and quantitative reverse transcriptase-PCR to localize prosaposin mRNA and protein.
• Auditory brainstem response and distortion product otoacoustic emissions testing in wild-type and prosaposin knockout mice.
• Histological analysis of the organ of Corti and immunofluorescence for neurite assessment.

Main Results:

• Prosaposin expression in the inner ear shifts from diffuse at birth to specific localization in hair cells and supporting cells by postnatal day 21.
• Prosaposin knockout mice exhibit progressive hearing loss starting around postnatal day 15-25 and reduced otoacoustic emissions.
• Histological analysis revealed cellular hypertrophy, hair cell loss, and abnormal neurite overgrowth in prosaposin knockout mice.

Conclusions:

• Prosaposin plays a vital role in maintaining the normal innervation patterns of the organ of Corti.
• The nAChR alpha10 subunit may also be involved in inner ear innervation, given its interaction with prosaposin and overlapping expression patterns.