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

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

Meniere's disease (MD) is a disorder of the inner ear characterized by chronic episodes of vertigo, tinnitus, increased aural pressure, and sensorineural hearing loss. Causes of MD are unknown, but endolymphatic hydrops is a hallmark. In addition, 5%–15% of MD cases have been identified as fami...

Full description

Saved in:
Bibliographic Details
Published in:The European journal of neuroscience Vol. 58; no. 3; pp. 2708 - 2723
Main Authors: Babu, Vidya, Bahari, Rose, Laban, Nora, Kulaga, Jacob, Abdul, Zahid, Zakkar, Basil, Al‐Najjar, Ahmad, Lesus, Joseph, Al‐Rifai, Abd‐al‐Rahman, Sattar, Heba, Irukulla, Suhitha, Gunniya, Pranav, Requena, Teresa, Lysakowski, Anna
Format: Journal Article
Language:English
Published: France Wiley Subscription Services, Inc 01-08-2023
Subjects:
Animal models
Auditory system
Autosomal dominant inheritance
Balance
Blood-brain barrier
Cytoskeleton
dtna
Factor analysis
fam136a
familial Meniere's disease
Genes
Genomes
Genotypes
Hearing loss
Inner ear
Meniere disease
Meniere's disease
Mutation
progressive hearing loss
Startle response
Synaptogenesis
Tinnitus
Variance analysis
vestibular
Vestibular system
familial Meniere's disease
dtna
progressive hearing loss
vestibular
fam136a
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Meniere's disease (MD) is a disorder of the inner ear characterized by chronic episodes of vertigo, tinnitus, increased aural pressure, and sensorineural hearing loss. Causes of MD are unknown, but endolymphatic hydrops is a hallmark. In addition, 5%–15% of MD cases have been identified as familial. Whole‐genome sequencing studies of individuals with familial MD identified DTNA and FAM136A as candidate genes for autosomal dominant inheritance of MD. Although the exact roles of these genes in MD are unknown, FAM136A encodes a mitochondrial protein, and DTNA encodes a cytoskeletal protein involved in synapse formation and maintenance, important for maintaining the blood–brain barrier. It is also associated with a particular aquaporin. We tested vestibular and auditory function in dtna and fam136a knockout (KO) mice, using RotaRod and startle reflex‐based clicker tests, respectively. Three‐factor analysis of variance (ANOVA) results indicated that sex, age, and genotype were significantly correlated with reduced mean latencies to fall (“latencies”) for male dtna KO mice, while only age was a significant factor for fam136a KO mice. Fam136a KO mice lost their hearing months before WTs (9–11 months vs. 15–20 months). In male dtna KO mice, divergence in mean latencies compared with other genotypes was first evident at 4 months of age, with older males having an even greater decrease. Our results indicate that fam136a gene mutations generate hearing problems, while dtna gene mutations produce balance deficits. Both mouse models should help to elucidate hearing loss and balance‐related symptoms associated with MD. This set of violin plots illustrates a key finding in the current paper, the poorer performance of older male dtna knockout mice (KO, blue) compared with female knockout mice (KO, pink), on the RotaRod test of balance, part of our results suggesting that dtna and fam136a, the two mouse mutants described in this paper, are candidates for Meniere's disease animal models.
Bibliography:Edited by: Antoine Adamantidis
Vidya Babu, Rose Bahari, and Nora Laban contributed equally.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0953-816X
1460-9568
DOI:10.1111/ejn.16083