scholarly journals Genetics of Peripheral Vestibular Dysfunction: Lessons from Mutant Mouse Strains

2014 ◽  
Vol 25 (03) ◽  
pp. 289-301 ◽  
Author(s):  
Sherri M. Jones ◽  
Timothy A. Jones
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Mouse Models ◽  
Noise Exposure ◽  
Mutant Mouse ◽  
Vestibular Dysfunction ◽  
Mouse Strains ◽  
Neural Function ◽  
Hereditary Hearing Loss ◽  
New Genes

Background: A considerable amount of research has been published about genetic hearing impairment. Fifty to sixty percent of hearing loss is thought to have a genetic cause. Genes may also play a significant role in acquired hearing loss due to aging, noise exposure, or ototoxic medications. Between 1995 and 2012, over 100 causative genes have been identified for syndromic and nonsyndromic forms of hereditary hearing loss. Mouse models have been extremely valuable in facilitating the discovery of hearing loss genes and in understanding inner ear pathology due to genetic mutations or elucidating fundamental mechanisms of inner ear development. Purpose: Whereas much is being learned about hereditary hearing loss and the genetics of cochlear disorders, relatively little is known about the role genes may play in peripheral vestibular impairment. Here we review the literature with regard to genetics of vestibular dysfunction and discuss what we have learned from studies using mutant mouse models and direct measures of peripheral vestibular neural function. Results: Several genes are considered that when mutated lead to varying degrees of inner ear vestibular dysfunction due to deficits in otoconia, stereocilia, hair cells, or neurons. Behavior often does not reveal the inner ear deficit. Many of the examples presented are also known to cause human disorders. Conclusions: Knowledge regarding the roles of particular genes in the operation of the vestibular sensory apparatus is growing, and it is clear that gene products co-expressed in the cochlea and vestibule may play different roles in the respective end organs. The discovery of new genes mediating critical inner ear vestibular function carries the promise of new strategies in diagnosing, treating, and managing patients as well as predicting the course and level of morbidity in human vestibular disease.

scholarly journals mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss

2021 ◽  
Vol 22 (12) ◽  
pp. 6368
Author(s):  
Maurizio Cortada ◽  
Soledad Levano ◽  
Daniel Bodmer
Keyword(s):  
Hearing Loss ◽  
Cell Survival ◽  
Inner Ear ◽  
Hearing Aids ◽  
Noise Exposure ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Curative Therapy ◽  
Age Related ◽  
Survival Pathways

Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Important treatment approaches for hearing loss include the development of regenerative therapies or the inhibition of cell death/promotion of cell survival pathways. The mammalian target of rapamycin (mTOR) pathway is a central regulator of cell growth, is involved in cell survival, and has been shown to be implicated in many age-related diseases. In the inner ear, mTOR signaling has also started to gain attention recently. In this review, we will emphasize recent discoveries of mTOR signaling in the inner ear and discuss implications for possible treatments for hearing restoration.

scholarly journals The Sound of Silence: Mouse Models for Hearing Loss

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sumantra Chatterjee ◽  
Thomas Lufkin
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hearing Impairment ◽  
Economic Loss ◽  
Signaling Cascades ◽  
Otic Vesicle ◽  
New Genes ◽  
Personal Loss ◽  
The Individual

Sensorineural hearing loss is one of the most common disabilities in humans. It is estimated that about 278 million people worldwide have slight to extreme hearing loss in both ears, which results in an economic loss for the country and personal loss for the individual. It is thus critical to have a deeper understanding of the causes for hearing loss to better manage and treat the affected individuals. The mouse serves as an excellent model to study and recapitulate some of these phenotypes, identify new genes which cause deafness, and to study their roles in vivo and in detail. Mutant mice have been instrumental in elucidating the function and mechanisms of the inner ear. The development and morphogenesis of the inner ear from an ectodermal layer into distinct auditory and vestibular components depends on well-coordinated gene expression and well-orchestrated signaling cascades within the otic vesicle and interactions with surrounding layers of tissues. Any disruption in these pathways can lead to hearing impairment. This review takes a look at some of the genes and their corresponding mice mutants that have shed light on the mechanism governing hearing impairment (HI) in humans.

scholarly journals Navigating Hereditary Hearing Loss: Pathology of the Inner Ear

2021 ◽  
Vol 15 ◽  
Author(s):  
Teresa Nicolson
Keyword(s):  
Hearing Loss ◽  
Animal Models ◽  
Inner Ear ◽  
Auditory System ◽  
Cranial Nerve ◽  
Hereditary Hearing Loss ◽  
Hearing Organ ◽  
Peripheral Auditory System ◽  
The Brain

Inherited forms of deafness account for a sizable portion of hearing loss among children and adult populations. Many patients with sensorineural deficits have pathological manifestations in the peripheral auditory system, the inner ear. Within the hearing organ, the cochlea, most of the genetic forms of hearing loss involve defects in sensory detection and to some extent, signaling to the brain via the auditory cranial nerve. This review focuses on peripheral forms of hereditary hearing loss and how these impairments can be studied in diverse animal models or patient-derived cells with the ultimate goal of using the knowledge gained to understand the underlying biology and treat hearing loss.

scholarly journals Mouse models of neurodegeneration: Know your question, know your mouse

2019 ◽  
Vol 11 (493) ◽  
pp. eaaq1818 ◽  
Author(s):  
Elizabeth M. C. Fisher ◽  
David M. Bannerman
Keyword(s):  
Neurodegenerative Disease ◽  
Mouse Models ◽  
Mutant Mouse ◽  
Mouse Strains ◽  
Disease Mechanisms ◽  
Research Questions

Many mutant mouse strains have been developed as models to investigate neurodegenerative disease in humans. However, variability in results among studies using these mouse strains has led to questions about the value of these models. Here, we appraise various mouse models for dissecting neurodegenerative disease mechanisms and emphasize the importance of asking appropriate research questions. In therapeutic studies, we suggest that understanding variability among and within mouse models is crucial for preventing translational failures in human patients.

scholarly journals Noise Induced Hearing Loss: A Case Study from a Speech-Language Pathologist’s Perspective

2021 ◽  
Author(s):  
Alejandro Brice
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hearing Aids ◽  
Noise Exposure ◽  
Chronic Health Condition ◽  
Noise Induced Hearing Loss ◽  
Speech Language Pathologist ◽  
The Individual ◽  
The U.S

Hearing loss is very common in the United States and the most widespread disability in the U.S. Hearing loss is the third most chronic health condition in the U.S. Noise induced hearing loss (NIHL) results from damaging external noise. This injury leads to temporarily or permanently affecting sensitive inner ear structures (e.g., cochlea, organ of Corti, and hair cells). NIHL can result from a single high-level noise exposure or repeated exposures to excessively loud noises [i.e., typically 85 dBA or greater, (A weighted decibel)]. Damage to the inner ear can also result from aging (i.e., presbycusis). This case study documents the hearing loss of an otherwise healthy 21-year-old, male individual and his progressive moderate-to-severe sensorineural hearing loss over a period of 41 years. His history will be reported along with his perspective as a speech-language pathologist and speech scientist. The individual with hearing loss has adapted to wearing hearing aids over the last five years. Issues that have occurred affecting comprehension along with compensatory strategies that assisted listening and comprehension will be discussed.

The inner ear

2009 ◽  
pp. 109-148
Author(s):  
Rogan Corbridge ◽  
Nicholas Steventon
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Sudden Hearing Loss ◽  
Structure And Function ◽  
Noise Induced Hearing Loss ◽  
Hereditary Hearing Loss ◽  
Syndromic Hearing Loss ◽  
And Function

Structure and function of the inner ear 110 Hearing loss 114 Presbyacusis 116 Noise-induced hearing loss 118 Idiopathic sudden hearing loss 120 Autoimmune ear disease 122 Ototoxicity 124 Hereditary hearing loss 126 Syndromic hearing loss I 128 Syndromic hearing loss II 130 Non-organic hearing loss (NOHL) ...

scholarly journals Research Progress on Flat Epithelium of the Inner Ear

2020 ◽  
pp. 775-785
Author(s):  
L HE ◽  
J-Y GUO ◽  
K LIU ◽  
G-P WANG ◽  
S-S GONG
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Noise Exposure ◽  
Sensory Epithelium ◽  
Sensorineural Hearing ◽  
Research Progress ◽  
Supporting Cells ◽  
Mesenchymal Transition

Sensorineural hearing loss and vertigo, resulting from lesions in the sensory epithelium of the inner ear, have a high incidence worldwide. The sensory epithelium of the inner ear may exhibit extreme degeneration and is transformed to flat epithelium (FE) in humans and mice with profound sensorineural hearing loss and/or vertigo. Various factors, including ototoxic drugs, noise exposure, aging, and genetic defects, can induce FE. Both hair cells and supporting cells are severely damaged in FE, and the normal cytoarchitecture of the sensory epithelium is replaced by a monolayer of very thin, flat cells of irregular contour. The pathophysiologic mechanism of FE is unclear but involves robust cell division. The cellular origin of flat cells in FE is heterogeneous; they may be transformed from supporting cells that have lost some features of supporting cells (dedifferentiation) or may have migrated from the flanking region. The epithelial-mesenchymal transition may play an important role in this process. The treatment of FE is challenging given the severe degeneration and loss of both hair cells and supporting cells. Cochlear implant or vestibular prosthesis implantation, gene therapy, and stem cell therapy show promise for the treatment of FE, although many challenges remain to be overcome.

Vestibular function in families with inherited autosomal dominant hearing loss

2008 ◽  
Vol 18 (1) ◽  
pp. 51-58
Author(s):  
Valerie A. Street ◽  
Jeremy C. Kallman ◽  
Paul D. Strombom ◽  
Naomi F. Bramhall ◽  
James O. Phillips
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Autosomal Dominant ◽  
Vestibular Function ◽  
Vestibular Dysfunction ◽  
Self Report ◽  
Vestibular Hypofunction ◽  
Mount Kilimanjaro ◽  
Vestibular Symptoms ◽  
Balance Problems

The inner ear contains the developmentally related cochlea and peripheral vestibular labyrinth. Given the similar physiology between these two organs, hearing loss and vestibular dysfunction may be expected to occur simultaneously in individuals segregating mutations in inner ear genes. Twenty-two different genes have been discovered that when mutated lead to non-syndromic autosomal dominant hearing loss. A review of the literature indicates that families segregating mutations in 13 of these 22 genes have undergone formal clinical vestibular testing. Formal assessment revealed vestibular dysfunction in families with mutations in ten of these 13 genes. Remarkably, only families with mutations in the COCH and MYO7A genes self-report considerable vestibular challenges. Families segregating mutations in the other eight genes do not self-report significant balance problems and appear to compensate well in everyday life for vestibular deficits discovered during formal clinical vestibular assessment. An example of a family (referred to as the HL1 family) with progressive hearing loss and clinically-detected vestibular hypofunction that does not report vestibular symptoms is described in this review. Notably, one member of the HL1 family with clinically-detected vestibular hypofunction reached the summit of Mount Kilimanjaro.

Bilateral progressive hearing loss and vestibular dysfunction with inner ear antibodies

2010 ◽  
Vol 37 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Kumiko Yukawa ◽  
Akira Hagiwara ◽  
Yasuo Ogawa ◽  
Nobuhiro Nishiyama ◽  
Shigetaka Shimizu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Vestibular Dysfunction ◽  
Progressive Hearing Loss
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