TMC1 and TMC2 Are Components of the Mechanotransduction Channel in Hair Cells of the Mammalian Inner Ear

SummarySensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells that expressed Tmc2 had high calcium permeability and large single-channel currents, while cells with mutant Tmc1 had reduced calcium permeability and reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad range of single-channel currents, suggesting multiple heteromeric assemblies of TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell transduction channels and contribute to permeation properties. Gradients in TMC channel composition may also contribute to variation in sensory transduction along the tonotopic axis of the mammalian cochlea

Gene Therapy Restores Auditory and Vestibular Function in a Mouse Model of Usher Syndrome Type 1c

Because there are currently no biological treatments for deafness, we sought to advance gene therapy approaches to treat genetic deafness. We reasoned that gene delivery systems that target auditory and vestibular sensory cells with high efficiency would be required to restore complex auditory and balance function. We focused on Usher Syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and used a knock-in mouse model, Ush1c c.216G>A, which carries a cryptic splice site mutation found in French-Acadian patients with Usher Syndrome type IC (USH1C). Following delivery of wild-type Ush1c into the inner ears of neonatal Ush1c c.216G>A mice, we find recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders

Inter-prismatic matrix structure characterization of mollusk shell and its effect on crystal formation

Mollusk biomineralization is an elaborate process in which cells, organic macromolecules, and calcium carbonate crystals are actively involved. Macromolecules (mainly are proteins and polysaccharide) act as a key role in regulating and limiting the size, orientation, polymorph and texture of inorganic phase. In this work, we focused on the inter-prismatic matrix of mollusk shell combining scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM) analytical techniques with CaCO3 recrystallization experiment to characterize its structure and effects on crystal formation. Our results show that the inter-prismatic matrix is not a sort of pure polymer, calcite nano-crystals are also located inside the inter-prismatic matrix. Interestingly, it seems that these nanocrystals have a preferred orientation, which means the inter-prismatic matrix do impose effect on the crystal formation. In vitro re-crystallization experiment using partially dissolved prismatic fragment as template indicates that the (104) faces of CaCO3 micro-crystals are closely associated with the walls of inter-prismatic matrix. Furthermore, a possible growth mechanism of mollusk shell prismatic layer was proposed