A potential acoustic role for CFTR ion channel in conductive hearing loss
Liyanage, P.; Mun, K.; Carraro, G.; Ogden, H. L.; Huang, Y.; Lee, J.; Ramananda, Y.; Stripp, B. R.; Arora, K.; Salomonis, N.; Hunter, L. L.; Naren, A. P.
Show abstract
Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). The middle ear and eustachian tube could be adversely affected in CF. In this study, we provide evidence of the role of CFTR function in conductive hearing. We developed an in-situ model to determine CFTR dependent fluid secretion in the middle ear using native mouse auditory capsule. A unique middle ear-on-a-chip was developed to address the functional and molecular basis of conductive hearing impairment. Using single-cell transcriptomics, middle ear cell composition and the associated transcriptomic signature were compared between CF and WT groups. A specialized subset of epithelial cells expressed CFTR with an overlapping signature with secretory epithelial cells. Genes related to ciliogenesis, hearing and ossification were significantly altered in CF mice middle ear. Our data suggest that CF middle ear may be at higher risk for conductive hearing loss.
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