Purchase this article with an account.
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/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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-/-).
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.
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.
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.
This PDF is available to Subscribers Only