Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice

Area of Science:

• Genetics
• Neuroscience
• Otolaryngology

Background:

• The shaker2 (sh2) mouse serves as a model for human non-syndromic deafness DFNB3, exhibiting profound deafness and abnormal circling behavior.
• Previous studies showed that a bacterial artificial chromosome (BAC) transgene carrying the Myo15a gene could restore hearing and abolish circling behavior in young transgenic animals.

Purpose of the Study:

• To investigate the long-term effects of BAC transgene correction on hearing and cochlear morphology in Myo15a mutant mice.
• To assess the impact of excess Myo15a expression on hearing in normal mice.

Main Methods:

• Myo15a mutant mice carrying the BAC transgene were analyzed at 2, 4, and 6 months of age.
• Hearing thresholds were evaluated and compared to age-matched controls.
• Cochlear morphology, specifically hair cell structure, was examined at the cellular level.

Main Results:

• Transgenic Myo15a mutant mice maintained normal hearing thresholds up to 6 months of age.
• Cochlear hair cell morphology was normal in the apical and upper basal turns, though some lower basal turn hair cells were absent in certain mutants.
• Excess Myo15a expression in normal mice did not significantly affect hearing function.

Conclusions:

• BAC transgene correction provides stable hearing function and maintains cochlear morphology in Myo15a mutant mice for at least 6 months.
• Myo15a gene dosage appears flexible, suggesting it may not be a critical factor for gene therapy efficacy in treating deafness.