scholarly journals CCDC154 Mutant Caused Abnormal Remodeling of the Otic Capsule and Hearing Loss in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Kai Xu ◽  
Xue Bai ◽  
Sen Chen ◽  
Le Xie ◽  
Yue Qiu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Spontaneous Mutation ◽  
Spiral Ganglion ◽  
Coiled Coil ◽  
Normal Structure ◽  
Mutant Mice ◽  
Spiral Ganglion Neuron ◽  
Otic Capsule ◽  
Related Gene ◽  
Homozygous Mutant

Osteopetrosis is a rare inherited bone disease characterized by dysfunction of osteoclasts, causing impaired bone resorption and remodeling, which ultimately leads to increased bone mass and density. Hearing loss is one of the most common complications of osteopetrosis. However, the etiology and pathogenesis of auditory damage still need to be explored. In this study, we found that a spontaneous mutation of coiled-coil domain-containing 154 (CCDC154) gene, a new osteopetrosis-related gene, induced congenital deafness in mice. Homozygous mutant mice showed moderate to severe hearing loss, while heterozygous or wild-type (WT) littermates displayed normal hearing. Pathological observation showed that abnormal bony remodeling of the otic capsule, characterized by increased vascularization and multiple cavitary lesions, was found in homozygous mutant mice. Normal structure of the organ of Corti and no substantial hair cell or spiral ganglion neuron loss was observed in homozygous mutant mice. Our results indicate that mutation of the osteopetrosis-related gene CCDC154 can induce syndromic hereditary deafness in mice. Bony remodeling disorders of the auditory ossicles and otic capsule are involved in the hearing loss caused by CDCC154 mutation.

scholarly journals Mechanism and Prevention of Spiral Ganglion Neuron Degeneration in the Cochlea

2022 ◽  
Vol 15 ◽  
Author(s):  
Li Zhang ◽  
Sen Chen ◽  
Yu Sun
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Stem Cell ◽  
Cell Therapy ◽  
Sensory Neurons ◽  
Stem Cell Therapy ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neuron ◽  
Regeneration Ability ◽  
Ganglion Neurons

Sensorineural hearing loss (SNHL) is one of the most prevalent sensory deficits in humans, and approximately 360 million people worldwide are affected. The current treatment option for severe to profound hearing loss is cochlear implantation (CI), but its treatment efficacy is related to the survival of spiral ganglion neurons (SGNs). SGNs are the primary sensory neurons, transmitting complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus. In mammals, SGNs have very limited regeneration ability, and SGN loss causes irreversible hearing loss. In most cases of SNHL, SGN damage is the dominant pathogenesis, and it could be caused by noise exposure, ototoxic drugs, hereditary defects, presbycusis, etc. Tremendous efforts have been made to identify novel treatments to prevent or reverse the damage to SGNs, including gene therapy and stem cell therapy. This review summarizes the major causes and the corresponding mechanisms of SGN loss and the current protection strategies, especially gene therapy and stem cell therapy, to promote the development of new therapeutic methods.

scholarly journals Inner Hair Cell and Neuron Degeneration Contribute to Hearing Loss in a Dfna2-Like Mouse Model

2018 ◽  
Author(s):  
Camila Carignano ◽  
Esteban Pablo Barila ◽  
Ezequiel Ignacio Rías ◽  
Leonardo Dionisio ◽  
Eugenio Aztiria ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Spiral Ganglion ◽  
Outer Hair Cells ◽  
Ganglion Neuron ◽  
Spiral Ganglion Neuron ◽  
Inner Hair Cell ◽  
Neuron Degeneration ◽  
Knock Out

HIGHLIGHTSKCNQ4 knock-out mouse shows hair cells and spiral ganglion neuron degeneration.Inner hair cells and spiral ganglion neuron loss begin 30 weeks later than outer hair cells in Kcnq4-/- mice.Inner hair cell loss kinetic is faster than that of outer hair cells in cochlear basal turn in Kcnq4-/-.Outer hair cells from Kcnq4-/- mice degenerate slower in apical than in basal turn.Kcnq4 knock-out allele expressed in C3H/HeJ strain reproduces the two phases of DFNA2 hearing loss.GRAPHICAL ABSTRACT

scholarly journals Minocycline Protection of Neomycin Induced Hearing Loss in Gerbils

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Alan M. Robinson ◽  
Irena Vujanovic ◽  
Claus-Peter Richter
Keyword(s):  
Hearing Loss ◽  
Spiral Ganglion ◽  
Hearing Threshold ◽  
Organ Of Corti ◽  
Aminoglycoside Antibiotic ◽  
Histological Evaluation ◽  
Spiral Ganglion Neuron ◽  
Spiral Ganglion Neurons ◽  
Simultaneous Application ◽  
Ganglion Neurons

This animal study was designed to determine if minocycline ameliorates cochlear damage is caused by intratympanic injection of the ototoxic aminoglycoside antibiotic neomycin. Baseline auditory-evoked brainstem responses were measured in gerbils that received 40 mM intratympanic neomycin either with 0, 1.2, or 1.5 mg/kg intraperitoneal minocycline. Four weeks later auditory-evoked brainstem responses were measured and compared to the baseline measurements. Minocycline treatments of 1.2 mg/kg and 1.5 mg/kg resulted in significantly lower threshold increases compared to 0 mg/kg, indicating protection of hearing loss between 6 kHz and 19 kHz. Cochleae were processed for histology and sectioned to allow quantification of the spiral ganglion neurons and histological evaluation of organ of Corti. Significant reduction of spiral ganglion neuron density was demonstrated in animals that did not receive minocycline, indicating that those receiving minocycline demonstrated enhanced survival of spiral ganglion neurons, enhanced survival of sensory hairs cells and spiral ganglion neurons, and reduced hearing threshold elevation correlates with minocycline treatment demonstrating that neomycin induced hearing loss can be reduced by the simultaneous application of minocycline.

scholarly journals A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 411
Author(s):  
María Lachgar ◽  
Matías Morín ◽  
Manuela Villamar ◽  
Ignacio del Castillo ◽  
Miguel Ángel Moreno-Pelayo
Keyword(s):  
Hearing Loss ◽  
Stop Codon ◽  
Coiled Coil ◽  
Premature Stop Codon ◽  
Scaffolding Protein ◽  
Common Mechanism ◽  
Chinese Family ◽  
Truncating Mutation ◽  
Spanish Family ◽  
Sensory Defect

Nonsyndromic hereditary hearing loss is a common sensory defect in humans that is clinically and genetically highly heterogeneous. So far, 122 genes have been associated with this disorder and 50 of them have been linked to autosomal dominant (DFNA) forms like DFNA68, a rare subtype of hearing impairment caused by disruption of a stereociliary scaffolding protein (HOMER2) that is essential for normal hearing in humans and mice. In this study, we report a novel HOMER2 variant (c.832_836delCCTCA) identified in a Spanish family by using a custom NGS targeted gene panel (OTO-NGS-v2). This frameshift mutation produces a premature stop codon that may lead in the absence of NMD to a shorter variant (p.Pro278Alafs*10) that truncates HOMER2 at the CDC42 binding domain (CBD) of the coiled-coil structure, a region that is essential for protein multimerization and HOMER2-CDC42 interaction. c.832_836delCCTCA mutation is placed close to the previously identified c.840_840dup mutation found in a Chinese family that truncates the protein (p.Met281Hisfs*9) at the CBD. Functional assessment of the Chinese mutant revealed decreased protein stability, reduced ability to multimerize, and altered distribution pattern in transfected cells when compared with wild-type HOMER2. Interestingly, the Spanish and Chinese frameshift mutations might exert a similar effect at the protein level, leading to truncated mutants with the same Ct aberrant protein tail, thus suggesting that they can share a common mechanism of pathogenesis. Indeed, age-matched patients in both families display quite similar hearing loss phenotypes consisting of early-onset, moderate-to-profound progressive hearing loss. In summary, we have identified the third variant in HOMER2, which is the first one identified in the Spanish population, thus contributing to expanding the mutational spectrum of this gene in other populations, and also to clarifying the genotype–phenotype correlations of DFNA68 hearing loss.

scholarly journals Tomographic diagnosis and relevant aspects of otosclerosis

2013 ◽  
Vol 46 (5) ◽  
pp. 307-312 ◽  
Author(s):  
Juliana Oggioni Gaiotti ◽  
Natália Delage Gomes ◽  
Ana Maria Doffémond Costa ◽  
Caroline Laurita Batista Couto Villela ◽  
Wanderval Moreira ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Hearing Loss ◽  
Differential Diagnosis ◽  
Multidetector Computed Tomography ◽  
Surgical Planning ◽  
Otic Capsule ◽  
Metabolic Derangement ◽  
Pictorial Essay ◽  
Temporal Bone Anatomy ◽  
Endochondral Layer

A literature review and pictorial essay were developed to discuss the importance of knowing the main findings and locations of otosclerosis at multidetector computed tomography (MDCT). The authors performed a retrospective review of cases of otosclerosis diagnosed in their institution by means of high resolution multidetector computed tomography. Otosclerosis corresponds to otic capsule dysplasia characterized by metabolic derangement of its endochondral layer. Such condition constitutes a relevant cause of sensorineural hearing loss, affecting about 7% to 10% of the general population. The diagnosis is usually clinical, but imaging methods play a significant role in the anatomical detailing, differential diagnosis, surgical planning and evaluation of postoperative complications. Among such methods, the relevance of MDCT is highlighted. Radiologists should be familiar with the MDCT findings of otosclerosis, as well as with the temporal bone anatomy to assist in the appropriate clinical management of this disease.

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