RotaRod and acoustic startle reflex performance of two potential mouse models for Meniere's disease

Area of Science:

• Genetics
• Neuroscience
• Otolaryngology

Background:

• Meniere's disease (MD) is an inner ear disorder with unknown causes, often featuring vertigo, tinnitus, and hearing loss.
• Familial forms of MD suggest a genetic component, with DTNA and FAM136A identified as candidate genes.
• The specific roles of DTNA and FAM136A in MD pathogenesis remain unclear.

Purpose of the Study:

• To investigate the functional roles of DTNA and FAM136A in auditory and vestibular systems.
• To establish mouse models for studying the genetic basis of Meniere's disease symptoms.

Main Methods:

• Generated knockout (KO) mice for dtna and fam136a genes.
• Assessed vestibular function using the RotaRod test.
• Evaluated auditory function via startle reflex-based clicker tests.
• Analyzed data using three-factor analysis of variance (ANOVA).

Main Results:

• Male dtna KO mice exhibited reduced latency to fall, indicating balance deficits, with effects significant for sex, age, and genotype.
• Fam136a KO mice showed age-dependent hearing loss, occurring earlier than in wild-type (WT) mice.
• DTNA mutations were linked to balance issues, while FAM136A mutations were associated with hearing impairment.

Conclusions:

• FAM136A gene mutations are implicated in hearing problems.
• DTNA gene mutations are linked to balance deficits.
• These mouse models provide valuable tools for understanding MD-related hearing loss and balance disorders.