Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C

David S Williams; Tomas S Aleman; Concepción Lillo; Vanda S Lopes; Louise C Hughes; Edwin M Stone; Samuel G Jacobson

doi:10.1167/iovs.08-3358

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Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C

Journal article

Open access

Peer reviewed

Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C

David S Williams, Tomas S Aleman, Concepción Lillo, Vanda S Lopes, Louise C Hughes, Edwin M Stone and Samuel G Jacobson

Investigative ophthalmology & visual science, Vol.50(8), pp.3881-3889

08/2009

DOI: 10.1167/iovs.08-3358

PMCID: PMC2893298

PMID: 19324851

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https://www.ncbi.nlm.nih.gov/pmc/articles/2893298View

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Abstract

To investigate the expression of harmonin in the mouse retina, test for ultrastructural and physiological mutant phenotypes in the retina of an Ush1c mutant mouse, and define in detail the retinal phenotype in human USH1C. Antibodies were generated against harmonin. Harmonin isoform distribution was examined by Western blot analysis and immunocytochemistry. Retinas of deaf circler (dfcr) mice, which possess mutant Ush1c, were analyzed by microscopy and electroretinography (ERG). Two siblings with homozygous 238_239insC (R80fs) USH1C mutations were studied with ERG, perimetry, and optical coherence tomography (OCT). Harmonin isoforms a and c, but not b are expressed in the retina. Harmonin is concentrated in the photoreceptor synapse where the majority is postsynaptic. Dfcr mice do not undergo retinal degeneration and have normal synaptic ultrastructure and ERGs. USH1C patients had abnormal rod and cone ERGs. Rod- and cone-mediated sensitivities and retinal laminar architecture were normal across 50 degrees -60 degrees of visual field. A transition zone to severely abnormal function and structure was present at greater eccentricities. The largest harmonin isoforms are not expressed in the retina. A major retinal concentration of harmonin is in the photoreceptor synapses, both pre- and post-synaptically. The dfcr mouse retina is unaffected by its mutant Ush1c. Patients with USH1C retained regions of normal central retina surrounded by degeneration. Perhaps the human disease is simply more aggressive than that in the mouse. Alternatively, the dfcr mouse may be a model for nonsyndromic deafness, due to the nonpathologic effect of its mutation on the retinal isoforms.

Immunohistochemistry

Phenotype

Retina - metabolism

Humans

Middle Aged

Child, Preschool

Male

Retinal Degeneration - metabolism

Microscopy, Immunoelectron

Protein Isoforms - metabolism

Mice, Mutant Strains

Adult

Female

Child

Siblings

Electroretinography

Photoreceptor Cells, Vertebrate - ultrastructure

Tomography, Optical Coherence

Mice, Inbred C57BL

Blotting, Western

Microscopy, Confocal

Animals

Carrier Proteins - metabolism

Adolescent

Mice

Mice, Inbred BALB C

Photoreceptor Cells, Vertebrate - metabolism

Adaptor Proteins, Signal Transducing - metabolism

Usher Syndromes - metabolism

Details

Title: Subtitle: Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C
Creators: David S Williams - University of California, Los Angeles
Tomas S Aleman
Concepción Lillo
Vanda S Lopes
Louise C Hughes
Edwin M Stone
Samuel G Jacobson
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.50(8), pp.3881-3889
DOI: 10.1167/iovs.08-3358
PMID: 19324851
PMCID: PMC2893298
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY007042 / NEI NIH HHS R01 EY007042-22 / NEI NIH HHS R01 EY007042-23A1 / NEI NIH HHS
Language: English
Date published: 08/2009
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980087402771

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