May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Retinal and Inner Ear Defects in Mice Lacking Nherf-1, a Potential New Model for Usher Syndrome
Author Affiliations & Notes
  • X. Sun
    Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
    The Berman-Gund Laboratory for the Study of Retinal Degenerations,
  • M. Adamian
    Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
    The Berman-Gund Laboratory for the Study of Retinal Degenerations,
  • B. S. Pawlyk
    Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
    The Berman-Gund Laboratory for the Study of Retinal Degenerations,
  • N. Michaud
    Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
    Howe Laboratory,
  • E. Weinman
    Departments of Medicine and Physiology, University of Maryland School of Medicine, Baltimore, Maryland
  • M. C. Liberman
    Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts
    Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • T. Li
    Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
    The Berman-Gund Laboratory for the Study of Retinal Degenerations,
  • Footnotes
    Commercial Relationships  X. Sun, None; M. Adamian, None; B.S. Pawlyk, None; N. Michaud, None; E. Weinman, None; M.C. Liberman, None; T. Li, None.
  • Footnotes
    Support  NIH Grants EY010309, R01 DC00188, NEI core grant P30 EY14104, and the Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2985. doi:https://doi.org/
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      X. Sun, M. Adamian, B. S. Pawlyk, N. Michaud, E. Weinman, M. C. Liberman, T. Li; Retinal and Inner Ear Defects in Mice Lacking Nherf-1, a Potential New Model for Usher Syndrome. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2985. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : NHERF-1 (Na+/H+ exchanger regulatory factor 1) is an adaptor protein containing tandem PDZ domains and was previously shown to be localized to the microvilli of retinal pigment epithelium (RPE). In the present study, we determined the subcellular localization of NHERF-1 in the retina and inner ear, and evaluated the potential defects in these two tissues in NHERF-1 knockout mice (NHERF-1-/-).

Methods: : Subcellular distribution of NHERF-1 in the retina and the inner ear was determined by immunofluorescence and immunoelectron microscopy. Structure and function of the retina and the inner ear in the NHERF-1 knockout mice were analyzed by light and electron microscopy, electroretinography (ERG), scanning electron microscopy and distortion product otoacoustic emissions (DPOAE) testing.

Results: : In the retina, NHERF-1 was concentrated at the RPE microvilli and along the apical processes of Muller glia. In the inner ear, NHERF-1 was associated with the stereocilia of outer hair cells, but was largely absent from the inner hair cells. In NHERF-1-/- mice, there was a loss of polarity in melanin granule distribution resembling the Ush1B mutant mouse. Photoreceptor degeneration was mild but noted in older NHERF-1-/- mice (at 23 months of age), as indicated by slight thinning of the outer nuclear layer and up-regulation of glial fibrillary acidic protein. Hearing loss was pronounced at 8 months of age as demonstrated by DPOAE testing. By histologic sectioning and scanning EM, there was disorganization of stereocilia and a loss of outer hair cells, which were more severe at the middle to basal turns.

Conclusions: : Despite its broad tissue distribution, loss of NHERF-1 results in a set of defects confined to the retina and the inner ear. These data suggest that the NHERF-1-/- mouse may be a useful model for studying human Usher syndrome. It is further postulated that certain mutations in the NHERF-1 gene in humans may be a cause of Usher syndrome.

Keywords: retinal degenerations: hereditary • retinal pigment epithelium • retinal glia 
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