Spontaneous Otoacoustic Emissions in<i>Tecta<sup>Y1870C/+</sup></i>Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane

Cheatham, Mary Ann; Zhou, Yingjie; Goodyear, Richard J.; Dallos, Peter; Richardson, Guy P.

doi:10.1523/eneuro.0314-18.2018

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…Threshold for tone bursts reflects the sound pressure level at which the ABR waveform (waves I–IV) disappears into the noise floor. Additional details are provided in our previous publications (Cheatham et al, 2014, 2018). Numbers of animals used of each age and their genotype were as follows: For ABRs: Ceacam16 +/+ (6–7m = 10, 12m = 11), Ceacam16 +/βgal (6–7m = 13, 12m = 11), Ceacam16 βgal/βgal (6–7m = 13, 12m = 12).…”

Section: Methodsmentioning

confidence: 99%

Accelerated Age-Related Degradation of the Tectorial Membrane in the Ceacam16βgal/βgal Null Mutant Mouse, a Model for Late-Onset Human Hereditary Deafness DFNB113

Goodyear

Cheatham

Naskar

et al. 2019

Front. Mol. Neurosci.

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CEACAM16 is a non-collagenous protein of the tectorial membrane, an extracellular structure of the cochlea essential for normal hearing. Dominant and recessive mutations in CEACAM16 have been reported to cause postlingual and progressive forms of deafness in humans. In a previous study of young Ceacam16 βgal/βgal null mutant mice on a C57Bl/6J background, the incidence of spontaneous otoacoustic emissions (SOAEs) was greatly increased relative to Ceacam16 +/+ and Ceacam16 +/βgal mice, but auditory brain-stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) were near normal, indicating auditory thresholds were not significantly affected. To determine if the loss of CEACAM16 leads to hearing loss at later ages in this mouse line, cochlear structure and auditory function were examined in Ceacam16 +/+ , Ceacam16 +/βgal and Ceacam16 βgal/βgal mice at 6 and 12 months of age and compared to that previously described at 1 month. Analysis of older Ceacam16 βgal/βgal mice reveals a progressive loss of matrix from the core of the tectorial membrane that is more extensive in the apical, low-frequency regions of the cochlea. In Ceacam16 βgal/βgal mice at 6–7 months, the DPOAE magnitude at 2f1-f2 and the incidence of SOAEs both decrease relative to young animals. By ∼12 months, SOAEs and DPOAEs are not detected in Ceacam16 βgal/βgal mice and ABR thresholds are increased by up to ∼40 dB across frequency, despite a complement of hair cells similar to that present in Ceacam16 +/+ mice. Although SOAE incidence decreases with age in Ceacam16 βgal/βgal mice, it increases in aging heterozygous Ceacam16 +/βgal mice and is accompanied by a reduction in the accumulation of CEACAM16 in the tectorial membrane relative to controls. An apically-biased loss of matrix from the core of the tectorial membrane, similar to that observed in young Ceacam16 βgal/βgal mice, is also seen in Ceacam16 +/+ and Ceacam16 +/βgal mice, and other strains of wild-type mice, but at much later ages. The loss of Ceacam16 therefore accelerates age-related degeneration of the tectorial membrane leading, as in humans with mutations in CEACAM16 , to a late-onset progressive form of hearing loss.

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Section: Methodsmentioning

confidence: 99%

Accelerated Age-Related Degradation of the Tectorial Membrane in the Ceacam16βgal/βgal Null Mutant Mouse, a Model for Late-Onset Human Hereditary Deafness DFNB113

Goodyear

Cheatham

Naskar

et al. 2019

Front. Mol. Neurosci.

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“…Although young mutants retain wild-type-like sensitivity (as assessed with ABR thresholds), they have reduced DPOAEs at 6–7 months of age, as do Tecta Y1870C/+ mice. In fact, both mutants show a partial loss of gain (as assessed ABR thresholds), yet the Tecta Y1870C/+ mice are prolific emitters ( 45 ), whereas the older mice lacking Ceacam16 are not.…”

Section: Resultsmentioning

confidence: 99%

Age-related degradation of tectorial membrane dynamics with loss of CEACAM16

Mansour

Sellon

Filizzola

et al. 2021

Biophysical Journal

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Studies of genetic disorders of sensorineural hearing loss have been instrumental in delineating mechanisms that underlie the remarkable sensitivity and selectivity that are hallmarks of mammalian hearing. For example, genetic modifications of TECTA and TECTB, which are principal proteins that comprise the tectorial membrane (TM), have been shown to alter auditory thresholds and frequency tuning in ways that can be understood in terms of changes in the mechanical properties of the TM. Here, we investigate effects of genetic modification targeting CEACAM16, a third important TM protein. Loss of CEACAM16 has been recently shown to lead to progressive reductions in sensitivity. Whereas age-related hearing losses have previously been linked to changes in sensory receptor cells, the role of the TM in progressive hearing loss is largely unknown. Here, we show that TM stiffness and viscosity are significantly reduced in adult mice that lack functional CEACAM16 relative to age-matched wild-type controls. By contrast, these same mechanical properties of TMs from juvenile mice that lack functional CEACAM16 are more similar to those of wild-type mice. Thus, changes in hearing phenotype align with changes in TM material properties and can be understood in terms of the same TM wave properties that were previously used to characterize modifications of TECTA and TECTB. These results demonstrate that CEACAM16 is essential for maintaining TM mechanical and wave properties, which in turn are necessary for sustaining the remarkable sensitivity and selectivity of mammalian hearing with increasing age.

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“…It may be anticipated that any mechanical discontinuity in the BM of Emilin2 −/− mice could generate spontaneous otoacoustic emissions (SOAEs) since deformity of the tectorial membrane, the other major extracellular membranous structure of the organ of Corti, produces SOAEs (27). However, SOAEs were not detected in Emilin2 −/− mice, suggesting that changes in the properties of the tectorial membrane rather than the BM cause the most disruption to energy exchange between the outer hair cells and other structures of the cochlear partition.…”

Section: Elevation Of Distortion Product Otoacoustic Emission and Aud...mentioning

confidence: 99%

Emilin 2 promotes the mechanical gradient of the cochlear basilar membrane and resolution of frequencies in sound

et al. 2020

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The detection of different frequencies in sound is accomplished with remarkable precision by the basilar membrane (BM), an elastic, ribbon-like structure with graded stiffness along the cochlear spiral. Sound stimulates a wave of displacement along the BM with maximal magnitude at precise, frequency-specific locations to excite neural signals that carry frequency information to the brain. Perceptual frequency discrimination requires fine resolution of this frequency map, but little is known of the intrinsic molecular features that demarcate the place of response on the BM. To investigate the role of BM microarchitecture in frequency discrimination, we deleted extracellular matrix protein emilin 2, which disturbed the filamentous organization in the BM. Emilin2−/− mice displayed broadened mechanical and neural frequency tuning with multiple response peaks that are shifted to lower frequencies than normal. Thus, emilin 2 confers a stiffness gradient on the BM that is critical for accurate frequency resolution.

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Spontaneous Otoacoustic Emissions inTecta^Y1870C/+Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane

Cited by 9 publications

References 51 publications

Accelerated Age-Related Degradation of the Tectorial Membrane in the Ceacam16βgal/βgal Null Mutant Mouse, a Model for Late-Onset Human Hereditary Deafness DFNB113

Accelerated Age-Related Degradation of the Tectorial Membrane in the Ceacam16βgal/βgal Null Mutant Mouse, a Model for Late-Onset Human Hereditary Deafness DFNB113

Age-related degradation of tectorial membrane dynamics with loss of CEACAM16

Emilin 2 promotes the mechanical gradient of the cochlear basilar membrane and resolution of frequencies in sound

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Spontaneous Otoacoustic Emissions inTectaY1870C/+Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane

Cited by 9 publications

References 51 publications

Accelerated Age-Related Degradation of the Tectorial Membrane in the Ceacam16βgal/βgal Null Mutant Mouse, a Model for Late-Onset Human Hereditary Deafness DFNB113

Accelerated Age-Related Degradation of the Tectorial Membrane in the Ceacam16βgal/βgal Null Mutant Mouse, a Model for Late-Onset Human Hereditary Deafness DFNB113

Age-related degradation of tectorial membrane dynamics with loss of CEACAM16

Emilin 2 promotes the mechanical gradient of the cochlear basilar membrane and resolution of frequencies in sound

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Spontaneous Otoacoustic Emissions inTecta^Y1870C/+Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane