Analysis of cochlear outer hair cell degeneration in a mouse model of DFNA2 deafness

CARIGNANO, C.; BARILA, E.P.; RIAS, E.; SPITZMAUL, G.

Mar del Plata

Congreso; XXXII Congress of the Argentine Society for Research in Neuroscience; 2017

Sociedad Argentina de Investigación en Neurociencias

DFNA2, a slowly progressive deafness, is characterized by sensorineural loss that starts affecting high frequencies and progresses across all frequencies. Mutations in KCNQ4 channel, the voltage-activated K+ channel expressed in outer hair cells (OHCs), are the main responsible factors for deafness, leading to cell death by unknown mechanisms. To analyze the role of KCNQ4 channel we used a mouse model that lacks its expression (KO mouse). Our aim is to determine OHCs degeneration over time analyzing cell death in different cochlear segments. We dissected cochleas from wild type (WT) and KO mice and analyzed by immunofluorescence the presence of OHCs in whole mount preparations. Our results indicated that at 4 weeks-old, the number of OHCs along the whole cochlear length decreased ~24% in KO compared to WT mice. The degenerative process progressed reaching 40% of cell loss at 8 weeks-old. OHCs loss was different depending on the cochlear turns: basal, middle and apical. We determined maximum degeneration of OHCs in the basal turn. In KO mice, at 8 weeks-old the number of OHCs in the basal fragment decreased 40% while it was ~25% in the other two fragments. Additionally, our preliminary analysis suggested that OHC loss was higher in the middle row than in the outer and inner rows. We concluded that cell death progresses at a rate of ~5% cell loss/week, starting at the basal turn, suggesting a higher expression or functionality of KNCQ4 channel in OHCs fromthe basal fragment.