Mutation of the TBCE gene causes disturbance of microtubules in the auditory nerve and cochlear outer hair cell degeneration accompanied by progressive hearing loss in the pmn/pmn mouse
| Autor: | Janos Groh, Andreas Radeloff, Rudolf Hagen, Robert Mlynski, Kristen Rak, Silke Frenz, Rudolf Martini, Sibylle Jablonka |
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| Rok vydání: | 2013 |
| Předmět: |
Hearing loss
Hearing Loss Sensorineural Biology Microtubules Mice Developmental Neuroscience Microtubule otorhinolaryngologic diseases medicine In Situ Nick-End Labeling Missense mutation Animals Motor Neuron Disease Cochlear Nerve Cochlea Motor neuron medicine.disease Immunohistochemistry Mice Mutant Strains Cell biology Electrophysiology Disease Models Animal Hair Cells Auditory Outer medicine.anatomical_structure Tubulin Neurology Mutation Nerve Degeneration biology.protein Sensorineural hearing loss sense organs Hair cell medicine.symptom Neuroscience Molecular Chaperones |
| Zdroj: | Experimental neurology. 250 |
| ISSN: | 1090-2430 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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