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Projekt
The role of LRBA (LPS-responsive, beige-like anchor protein) in auditory function
Antragstellerin
Professorin Dr. Nicola Strenzke
Fachliche Zuordnung
Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Förderung
Förderung von 2012 bis 2016
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 218178433
LRBA (LPS-responsive, beige-like anchor protein) belongs to the BEACH protein family, members of which are involved in intracellular protein trafficking and in pre- and postsynaptic function. We demonstrated that LRBA is expressed in inner and outer hair cells, the spiral ligament, and in marginal cells of the stria vascularis. LRBA knockout mice were found to have moderate to severe hearing loss, as assessed by auditory brainstem responses (ABR) and startle responses. Further preliminary systems and cell physiological data suggest a hair cell dysfunction that combines a deficit of transduction currents and synaptic transmission. To further differentiate the mechanism of hearing loss in LRBA knockout mice, we plan to record ABRs at different mouse ages and to measure the endocochlear potential and endolymphatic potassium concentration. We will study the morphology and FM 1-43 uptake of hair cell stereocilia in young animals and assess inner hair cell presynaptic function by patch clamp experiments and, if needed hair cell transduction currents and outer hair cell electromotility. Effects of LRBA disruption on signal encoding in the auditory pathway will be examined both by single auditory nerve fiber recordings and by behavioral testing. Our data will also help to better understand the molecular and cell biological function of LRBA and of BEACH proteins in general.
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