Abstract
The progressive motor neuronopathy (pmn/pmn) mouse, an animal model for a fast developing human motor neuron disorder, is additionally characterized by simultaneous progressive sensorineural hearing loss. The gene defect in the pmn/pmn mouse is localized to a missense mutation in the tubulin-specific chaperone E (TBCE) gene on mouse chromosome 13, which is one of the five tubulin-specific chaperons involved in tubulin folding and dimerization. The missense mutation leads to a disturbance of tubulin structures in the auditory nerve and a progressive outer hair cell loss due to apoptosis, which is accompanied by highly elevated ABR-thresholds and loss of DPOAEs. In addition the TBCE protein is selectively expressed in the outer hair cells and the transcellular processes of the inner pillar cells in the cochlea of control and pmn/pmn mouse. We conclude from our study that the mutation of the TBCE gene affects the auditory nerve and the cochlear hair cells simultaneously, leading to progressive hearing loss. This animal model will give the chance to test possible therapeutic strategies in special forms of hearing loss, in which the auditory nerve and the cochlear hair cells are simultaneously affected.