EHD1 is a member of four Eps15 homology domain proteins and has been shown to be part of the endocytic recycling machinery and ciliogenesis. It is involved in the recycling of several receptors, such as transferrin I, glucose transporter type 4 (GLUT4), and insulin-like growth factor 1 receptor (IGFR1) and has been implicated in the remodelling of connexin 43 gap junctions in the heart. A founder mutation in EHD1 presenting with sensorineural hearing loss in patients indicates a role of EHD1 in the process of hearing and its consideration as a novel hearing loss gene. This study aimed to identify the role of EHD1 in the process of hearing in mice and the pathophysiology of EHD1-related hearing impairment. Therefore, the localisation as well as underlying mechanisms of hearing loss due to the inactivation of EHD1 were examined in an EHD1-/- mouse model. Frequency-dependent auditory brainstem response (F-ABR) measurements revealed hearing loss of EHD1-/- mice and
histological analysis of murine cochleae showed Ehd1 to be localised within the stria vascularis. No alterations in expression levels or localisation of essential transporters were observed due to the loss of Ehd1. However, degeneration of marginal and intermediate cells of the stria vascularis was observed via transmission electron micrographs of EHD1-/- striae. In addition, alterations in gene expression patterns indicated an ongoing inflammatory response within the stria vascularis. Proteome and
transcriptome analyses of murine stria vascularis pointed towards the disruption of
pericytes in EHD1-/- animals with significantly upregulated proteins typically found in
this cell type. Proteome analysis also revealed the significant upregulation of connexin
43 in Ehd1-deficient striae. In the stria vascularis, connexin 43 is important for the
generation of the endolymphatic potential (EP) and its absence is known to cause
hearing loss. In addition, pericytes are known to form gap junctions with endothelial
cells consisting of connexin 43. Taken together, the results obtained from
morphological and functional studies suggest the degeneration of the stria vascularis
with a possible disturbance of connexin 43 gap junctions and strial pericyte
dysfunction. Further studies are required to determine the chain of events. Whether a
dysfunction of pericytes, a disruption of gap junction remodelling processes or another
underlying condition is responsible for the phenotype observed in this study remains
to be investigated.

EHD1 ist ein Mitglied von vier Eps15 homology domain Proteinen und beteiligt an der endozytotischen Recycling Maschinerie und der Ziliogenese. Es ist involviert in Recycling-Prozessen verschiedener Rezeptoren, wie dem Transferrin I Rezeptor, dem Glucose Transporter Typ 4 (GLUT4) und dem Insulin-like growth factor 1 receptor (IGFR1). Zudem wird ihm eine Aufgabe im Remodelling von Connexin 43 Gap junctions in Kardiomyozyten zugeschrieben. Eine Mutation im EHD1 Gen führt zu sensorineuralem Hörverlust bei Patienten, was darauf hinweist, dass EHD1 am Hörvermögen beteiligt ist. Diese Arbeit zielte darauf ab, die Rolle von EHD1 im Innenohr der Maus zu identifizieren und die Pathophysiologie von EHD1-bedingtem Hörverlust zu untersuchen.