Effect of conditional knockout of the TBCE gene in the outer hair cells of the cochlea

The TBCE gene codes for tubulin specific chaperone E (TBCE), which is involved in microtubule synthesis. The hearing loss in patients suffering from Kenny-Caffey syndrome is attributed to a mutation in the TBCE gene. In addition, progressive hearing loss has been observed in the mouse model of progressive motor neuropathy, which is caused by a mutation of the TBCE gene. Examinations revealed a progressive loss of the outer hair cells (OHC), but also a secondary neuropathy. Taken together, this supports the suggestion that TBCE is essential for the development and the functional integrity of the OHC. To investigate this further, a cell-specific conditional knockout of the TBCE gene in outer hair cells was generated using an inducible Cre-loxP system. Cre induction was performed at different time points to investigate postnatal development of the organ of Corti on the one hand and the maintenance of functionality after already completed development of the organ of Corti on the other hand. The effects of the loss of TBCE were evaluated by means of audiometry and subsequent immunohistochemical investigations. Measurements of otoacoustic emissions revealed evidence of outer hair cell dysfunction and brainstem audiometry demonstrated a significant increase in hearing thresholds. Hair cell counts showed no evidence of OHC loss. Further histological and molecular biological experiments should shed light on the underlying pathology, with a focus on the integrity of the OHC. The aim of the work is to gain insight into the specific function of TBCE for both development and maintenance of function of the organ of Corti. In addition, we expect that the results will lead to a better understanding of the mechanisms of hearing loss in patients with Kenny-Caffey syndrome.

Publication History

Article published online:
12 May 2023