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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http://dx.doi.org/10.1016/j.bpj.2021.09.029 | DOI Listing |
J Orthop Case Rep
December 2024
Department of Spine Surgery, Children Hospital Westmead, Sydney, Australia.
Introduction: Death is the most common outcome of longitudinal atlanto-occipital dissociation (L-AOD). Even though rare, survival is commonly seen in the pediatric population. This study reports a successful outcome of a pediatric patient with an L-AOD without neurodeficits, immobilized in a visor (head-neck-chest) orthosis.
View Article and Find Full Text PDFDev Cell
December 2024
Department of Neurobiology, University of Utah, Salt Lake City, UT, USA. Electronic address:
The apical extracellular matrix (aECM), organized by polarized epithelial cells, exhibits complex structures. The tectorial membrane (TM), an aECM in the cochlea mediating auditory transduction, exhibits highly ordered domain-specific architecture. α-Tectorin (TECTA), a glycosylphosphatidylinositol (GPI)-anchored ECM protein, is essential for TM organization.
View Article and Find Full Text PDFJ Comp Neurol
December 2024
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
A gene cadre orchestrates the normal development of sensory and non-sensory cells in the inner ear, segregating the cochlea with a distinct tonotopic sound frequency map, similar brain projection, and five vestibular end-organs. However, the role of genes driving the ear development is largely unknown. Here, we show double deletion of the Iroquois homeobox 3 and 5 transcription factors (Irx3/5 DKO) leads to the fusion of the saccule and the cochlear base.
View Article and Find Full Text PDFAnn Biomed Eng
December 2024
School of Biomedical Engineering, University of Oklahoma, Norman, OK, 73019, USA.
Biogerontology
November 2024
Department of Otolaryngology & Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin 2nd Road, Shanghai, 200025, China.
Age-related hearing loss (ARHL) is a common disease among the elderly. Although its pathogenesis remains unclear by now, it is widely accepted that ARHL is associated with the degenerative alterations within each component of the cochlea. Extracellular matrix (ECM) plays a crucial role in cochlear structure and function, providing not only structural support but also participating in vital physiological processes including the development, differentiation, survival of auditory sensory cells, and sound perception.
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