| First Author | Stalmann U | Year | 2021 |
| Journal | Front Cell Neurosci | Volume | 15 |
| Pages | 677543 | PubMed ID | 34335185 |
| Mgi Jnum | J:309698 | Mgi Id | MGI:6730777 |
| Doi | 10.3389/fncel.2021.677543 | Citation | Stalmann U, et al. (2021) Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9. Front Cell Neurosci 15:677543 |
| abstractText | Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out (Otof (-/-)) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average approximately 15 synapses per inner hair cell (IHC) in Otof (-/-) cochleae as well as in wild-type controls. Further on, the number of synapses in Otof (-/-) IHCs was reduced to approximately 7 at 8 weeks of age and to approximately 6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof (-/-) animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof (-/-) mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients. |
