Increased Spontaneous Otoacoustic Emissions in Mice with a Detached Tectorial Membrane

Abstract

Mutations in genes encoding tectorial membrane (TM) proteins are a significant cause of human hereditary hearing loss , and several mouse models have been developed to study the functional significance of this accessory structure in the mammalian cochlea. In this study, we use otoacoustic emissions (OAE), signals obtained from the ear canal that provide a measure of cochlear function, to characterize a mouse in which the TM is detached from the spiral limbus due to an absence of otoancorin (Otoa, Lukashkin et al. 2012). Our results demonstrate that spontaneous emissions (SOAE), sounds produced in the cochlea without stimulation, increase dramatically in mice with detached TMs even though their hearing sensitivity is reduced. This behavior is unusual because wild-type (WT) controls are rarely spontaneous emitters. SOAEs in mice lacking Otoa predominate around 7 kHz, which is much lower than in either WT animals when they generate SOAEs or in mutant mice in which the TM protein Ceacam16 is absent (Cheatham et al. 2014). Although both mutants lack Hensen's stripe, loss of this TM feature is only observed in regions coding frequencies greater than~15 kHz in WT mice so its loss cannot explain the low-frequency, de novo SOAEs observed in mice lacking Otoa. The fact that~80 % of mice lacking Otoa produce SOAEs even when they generate smaller distortion product OAEs suggests that the active process is still functioning in these mutants but the system(s) involved have become less stable due to alterations in TM structure.

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

“…Second, because the main body of the TM in Tecta Y1870C/+ mice has little physical contact with the organ of Corti due to delamination of Kimura’s membrane, the TM can no longer provide its normal load to and mechanical influence on the hair bundles of OHCs (Ó Maoiléidigh et al, 2012; Salvi et al, 2015). As a result, SOAEs are observed similar to other TM mutants where internal oscillations are also detected (Cheatham et al, 2014, 2016). We thus suggest that while the principal function of the TM as a whole is to stabilize the high-gain feedback system, its subcomponent, Kimura’s membrane, by itself, is essential for OHC mechanoelectrical transduction by virtue of its intimate contact with the tips of the OHC stereocilia.…”

“…Inasmuch as previously characterized TM mutants lacking either CEACAM16 (Cheatham et al, 2014) or OTOA (Cheatham et al, 2016) displayed an increase in SOAEs, we initially assayed for this type of emission, as shown in Figure 2. Here SOAE spectra are provided for 3 of the 20 wild-type Tecta +/+ mice that had recordable SOAEs and for 32 of the 51 heterozygous Tecta Y1870C/+ mice with SOAEs.…”

“…The TM is part of an amplifying, mechanical feedback loop in which OHCs function as prestin-actuated motors (Zheng et al, 2000). When the internal dynamics within the feedback loop are altered, loop gain can be maintained, but stability decreases and SOAEs emerge (Cheatham et al, 2014, 2016). In other words, genetically induced changes to TM properties alter the balance among individual components of this tightly coupled feedback system.…”

“…The latter was not observed for the suppressor levels reported here. Further details are provided in previous publications (Cheatham et al, 2014, 2016).…”

“…In the absence of CEACAM16, the striated-sheet matrix does not form, Hensen’s stripe is absent and large holes appear, especially in the apical portion of the TM. Furthermore, 79% of Otoa EGFP/EGFP mice (34 of 43 homozygotes) lacking OTOANCORIN (OTOA), in which the TM is detached from the limbus, also produce SOAEs (Cheatham et al, 2016). Because of the human hearing problems associated with TM defects and the unusual phenotype discovered in Ceacam16 βgal/βgal and Otoa EGFP/EGFP mice, we examined emissions and auditory brainstem responses (ABRs) in Tecta Y1870C/+ mice and their wild-type (WT) controls.…”