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OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear

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Abstract

Autosomal dominant optic atrophy (adOA) is the most common form of hereditary optic neuropathy. The majority of cases are associated with mutations in the OPA1 gene. A few cases of adOA are known to be associated with moderate progressive hearing loss. To gain insight into the pathogenesis of this hearing loss, we performed expression analyses of OPA1 in the rat auditory and vestibular organ. In cochlear tissue, several splice variants of OPA1 were detected, which are also expressed in retinal tissue. OPA1 mRNA and protein was found in the hair cells and ganglion cells of the cochlea and vestibular organ. In ganglion cells, OPA1 mRNA and protein was already detectable at birth, whereas in the organ of Corti OPA1 mRNA and protein was up-regulated after birth and reached mature-like expression level during the onset of hearing. Comparison of an antibody directed to the mitochondrial marker protein HSP60 with antibodies directed to different amino acid stretches of OPA1 revealed a sub-cellular distribution of OPA1 in areas of significant density of mitochondria. The data suggest that defects in OPA1 cause hearing disorders due to a progressing metabolic disturbance of hair and ganglion cells in the inner ear.

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Abbreviations

adOA:

Autosomal dominant optic atrophy

OHC:

Outer hair cell

IHC:

Inner hair cell

VHC:

Vestibular hair cell

SG:

Spiral ganglion cell

VG:

Vestibular ganglion cell

P:

Postnatal day

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Acknowledgments

The authors are grateful to Dr. Guy Lenears for providing the OPA1-II antibody and to Karin Rohbock for excellent technical assistance. We are very thankful for English revision of the manuscript by Dr. Rama Panford-Walsh. This work was supported by the Fritz Thyssen Stiftung für Wissenschaftsförderung, Köln, Germany and the Deutsche Forschungsgemeinschaft DFG KN316/4–1.

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Authors and Affiliations

  1. Molecular Genetics Laboratory, University Eye Hospital, Röntgenweg 11, 72076, Tübingen, Germany

    Stefanie Bette & Bernd Wissinger

  2. Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), Laboratory of Molecular Neurobiology and Cell Biology of the Inner Ear, University of Tübingen, Elfriede-Aulhorn-Straße 5, 72076, Tübingen, Germany

    Ulrike Zimmermann & Marlies Knipper

  3. Universitäts-HNO-Klinik, Elfriede-Aulhorn-Straße 5, 72076, Tübingen, Germany

    Marlies Knipper

Authors
  1. Stefanie Bette
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  2. Ulrike Zimmermann
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  3. Bernd Wissinger
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  4. Marlies Knipper
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Corresponding author

Correspondence to Marlies Knipper.

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Stefanie Bette and Ulrike Zimmermann contributed equally to this work.

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Bette, S., Zimmermann, U., Wissinger, B. et al. OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear. Histochem Cell Biol 128, 421–430 (2007). https://doi.org/10.1007/s00418-007-0321-7

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