MYO7a is required for the functional integrity of the mechanoelectrical transduction complex in the outer hair cells of the adult cochlea.
Myosin-VIIA (MYO7A) in an unconventional myosin responsible for syndromic (Usher 1B) or non-syndromic recessive deafness in humans when mutated. In the cochlea, MYO7A is expressed in the stereocilia of both inner and outer hair cells, where it is believed to act as the motor protein tensioning the mechanoelectrical transducer (MET) channel. Whether this tensioning role is a common feature among both types of cochlear hair cells is unknown. Here we show that MYO7A has a distinct role in adult outer hair cells (OHCs), being crucial for the structural integrity of the MET complex. Postnatal deletion of MYO7A did not affect the staircase structure of the hair bundles but caused a progressive reduction of the size of the MET current without affecting the resting open probability and calcium sensitivity of the MET channel. The hair bundle of OHCs deficient in MYO7A also showed reduced bundle stiffness and was highly susceptible to noise exposure. RNA-sequencing identified the down-regulation of several stereociliary proteins in the Myo7a-deficient cochlea. This study reveals that IHCs and OHCs use different mechanisms to maintain the MET channel in its most sensitive resting open position, and confirms that in OHCs,  this mechanism is MYO7A independent. Overall design: For the conditional knockout mice (Myo7afl/flMyo15-cre+/-), the targeted tm1a allele for Myo7a (Myo7atm1a(EUCOMM)Wtsi allele ID: 4431921) was generated by the Mouse Genetics Programme at the Wellcome Trust Sanger Institute (Cambridge, UK). For Myo7a the critical exons 10 and 11 were floxed and the tm1c allele was obtained by crossing the tm1a mouse to a FLPeR carrying mouse (Rosa26Fki). The tm1d alleles, which were used for the experiments, were obtained by crossing the tm1c mouse (Myo7afl/fl) with the Myo15-cre mice. For experiments littermate control Myo7afl/flMyo15-cre+/+ (referred in the manuscript as Myo7afl/fl) and knockout mice (Myo7afl/flMyo15-cre+/-) were used.