A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss that Contributes to Age-Related Hearing Loss in Mice

Peguero, Braulio; Tempel, Bruce L.

doi:10.1007/s10162-015-0519-7

Cited by 8 publications

(4 citation statements)

References 47 publications

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“…PCR of tail tissue samples performed genotyping. Transgene was generated on mixed C57/B6 and backcrossed into a CBA-CaJ (CBA) background after 12 generations to reduce accelerated progressive hearing loss (Peguero and Tempel, 2015; Sergeyenko et al, 2013; Willott and Erway, 1998). Results of RT-PCR from the three groups of animals, including wild-type littermates ( Cldn9 +/+ ) , heterozygote (Cldn9 +/T ), and Homozygous ( Cldn9 T/T ) with (1mg/ml) and without dox treatment.…”

Section: Resultsmentioning

confidence: 99%

Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

Chen,

Lee,

et al. 2023

Preprint

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Hearing loss is the most common form of sensory deficit. It occurs predominantly due to hair cell (HC) loss. Mammalian HCs are terminally differentiated by birth, making HC loss incurable. Here, we show the pharmacogenetic downregulation of Cldn9, a tight junction protein, generates robust supernumerary inner HCs (IHCs) in mice. The putative ectopic IHCs have functional and synaptic features akin to typical IHCs and were surprisingly and remarkably preserved for at least fifteen months >50% of the mouse’s life cycle. In vivo, Cldn9 knockdown using shRNA on postnatal days (P) P1-7 yielded analogous functional putative ectopic IHCs that were equally durably conserved. The findings suggest that Cldn9 levels coordinate embryonic and postnatal HC differentiation, making it a viable target for altering IHC development pre- and post-terminal differentiation.

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Section: Resultsmentioning

confidence: 99%

Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

Chen,

Lee,

et al. 2023

Preprint

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“…However, the threshold shifts seen here were drastically different than those found with a similar tobramycin dosing experiment in Swiss-Webster mice ( Gu et al, 2020 ). While little is reported on the susceptibility of ototoxicity for most strains of mice, the CBA/Ca is well known for its relative resistance to noise- ( Davis et al, 2001 ), and age- ( Zheng et al, 1999 ; Peguero and Tempel, 2015 ; Liu et al, 2019 ), related hearing loss. When comparing these studies, it seems the CBA/Ca mouse has more resistant to AG-ototoxicity.…”

Section: Discussionmentioning

confidence: 99%

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Longenecker¹,

Gu²,

Homan³

et al. 2021

Front. Mol. Neurosci.

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Aminoglycosides (AG) antibiotics are a common treatment for recurrent infections in cystic fibrosis (CF) patients. AGs are highly ototoxic, resulting in a range of auditory dysfunctions. It was recently shown that the acoustic startle reflex (ASR) can assess behavioral evidence of hyperacusis and tinnitus in an amikacin cochleotoxicity mouse model. The goal of this study was to establish if tobramycin treatment led to similar changes in ASR behavior and to establish whether ebselen can prevent the development of these maladaptive neuroplastic symptoms. CBA/Ca mice were divided into three groups: Group 1 served as a control and did not receive tobramycin or ebselen, Group 2 received tobramycin (200 mg/kg/s.c.) and the vehicle (DMSO/saline/i.p.) daily for 14 continuous days, and Group 3 received the same dose/schedule of tobramycin as Group 2 and ebselen at (20 mg/kg/i.p.). Auditory brainstem response (ABR) and ASR hearing assessments were collected at baseline and 2, 6, 10, 14, and 18 weeks from the start of treatment. ASR tests included input/output (I/O) functions which assess general hearing and hyperacusis, and Gap-induced prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus. At 18 weeks, histologic analysis showed predominantly normal appearing hair cells and spiral ganglion neuron (SGN) synapses. Following 14 days of tobramycin injections, 16 kHz thresholds increased from baseline and fluctuated over the 18-week recovery period. I/O functions revealed exaggerated startle response magnitudes in 50% of mice over the same period. Gap detection deficits, representing behavioral evidence of tinnitus, were observed in a smaller subset (36%) of animals. Interestingly, increases in ABR wave III/wave I amplitude ratios were observed. These tobramycin data corroborate previous findings that AGs can result in hearing dysfunctions. We show that a 14-day course of tobramycin treatment can cause similar levels of hearing loss and tinnitus, when compared to a 14-day course of amikacin, but less hyperacusis. Evidence suggests that tinnitus and hyperacusis might be common side effects of AG antibiotics.

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“…Their results suggest that DPOAE can be used to monitor hair cell function more accurately at specific anatomical locations than can the other methods. Peguero et al (40) assessed hearing with both methods in different mouse strains (CBA/CaJ, 129S6/SvEvTac and 101/H). They determined that DPOAE detect early-onset OHC dysfunction despite normal ABR thresholds.…”

Section: Discussionmentioning

confidence: 99%

Functional and morphological analysis of different aminoglycoside treatment regimens inducing hearing loss in mice

et al. 2019

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Aminoglycoside ototoxicity is common in clinical practice but reliable protective agents currently do not exist. Aminoglycoside regimens causing ototoxicity in different laboratory animals are under investigation. The assessment method used most commonly to determine auditory effects is the auditory brainstem response (ABR). Distortion product otoacoustic emissions (DPOAE) have been used less frequently. A precise recommendation on the specific method to assess peripheral auditory function before and after aminoglycoside toxicity in mice does not exist. In order to evaluate various mouse models for ototoxic injury caused by various aminoglycoside regimens, there is a need for performing preliminary tests in small cohorts before large experiments. The aim of our study was to investigate different aminoglycoside regimens that cause substantial ototoxic damage in vivo . Aminoglycosides are safe and produce a detectable hearing threshold shift in a small cohort of mice that can be used as a model for preliminary tests. Different ototoxic regimens were assessed by ABR and DPOAE measurements pre- and post-treatment. Further, the sensory cell loss was quantified by counting hair cells in the cochlea. It was revealed that an ototoxic regimen with kanamycin twice daily for 15 consecutive days is safe, well tolerated and produces an early significant hearing threshold shift detected by DPOAE in a small cohort of mice. The study compared ABR and DPOAE in mentioned regimens for the first time and illustrated that DPOAE is well suited for detecting hearing threshold shifts in high frequencies before ABR threshold shifts occur in accordance with predominating outer hair cell damage mainly in the basal turn of the cochlea.

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A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss that Contributes to Age-Related Hearing Loss in Mice

Cited by 8 publications

References 47 publications

Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Functional and morphological analysis of different aminoglycoside treatment regimens inducing hearing loss in mice

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