The Role of Thyroid Hormone Transporters Mct8 and Oatp1c1 in Cochlear Myelination and Ossicle Bone Development

Thyroid hormones (TH) are essential for the development of multiple organ systems, including the auditory system. Adequate TH levels are required before the onset of auditory function to ensure optimal development, and disruptions in TH signaling can lead to irreversible auditory deficits. The Allan-Herndon-Dudley Syndrome (AHDS) is an X-linked disorder caused by mutations in the SLC16A2 gene encoding the monocarboxylate transporter 8 (MCT8). Previous work in our lab showed that mice phenocopying AHDS, generated by knocking out both the Mct8 and Oatp1c1 transporters, display abnormal hearing. Here, we studied the individual and combined roles of Mct8 and Oatp1c1 in auditory development and determine how their deficiency affects cochlear myelination and ossicle bone development. RT-qPCR results demonstrated a significant increase in the mRNA expression of myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) in dKO mice compared to wild-type controls at postnatal day 14 (P14). However, no significant differences were observed in MBP or MOG expression at P60. MPZ expression was not significantly different at any age. Furthermore, cell count of the transition zone for both Oligodendrocytes and Schwann cells did not present any significant differences between the groups at either timepoint. These results suggest an upregulation of oligodendrocyte precursor cells in the transition zone of the cochlear nerve while there is a downregulation of mature oligodendrocytes. Ossicle measurements revealed an enlargement of the bones at P60. Together these results suggest that the auditory abnormalities previously found in dKO mice may be caused by a combination of myelin and ossicle abnormalities.