PUBLICATION
myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses
- Authors
- Wasfy, M.M., Matsui, J.I., Miller, J., Dowling, J.E., Perkins, B.D.
- ID
- ZDB-PUB-140513-219
- Date
- 2014
- Source
- Experimental Eye Research 122: 65-76 (Journal)
- Registered Authors
- Perkins, Brian
- Keywords
- ERG, Myo7a, Ush1B, Usher Syndrome, photoreceptor, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Death
- Codon, Nonsense*
- Dark Adaptation
- Disease Models, Animal
- Electroretinography
- Immunohistochemistry
- In Situ Nick-End Labeling
- Light
- Melanosomes/physiology
- Microscopy, Electron, Transmission
- Myosins/genetics*
- Nystagmus, Optokinetic/physiology
- Photoreceptor Cells, Vertebrate/metabolism
- Photoreceptor Cells, Vertebrate/pathology*
- Retinal Degeneration/genetics*
- Retinal Degeneration/metabolism
- Retinal Degeneration/physiopathology
- Retinal Rod Photoreceptor Cells/metabolism
- Rod Opsins/metabolism
- Usher Syndromes/genetics
- Usher Syndromes/metabolism
- Usher Syndromes/pathology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- PubMed
- 24698764 Full text @ Exp. Eye. Res.
Citation
Wasfy, M.M., Matsui, J.I., Miller, J., Dowling, J.E., Perkins, B.D. (2014) myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses. Experimental Eye Research. 122:65-76.
Abstract
Mutations in myosin VIIa (MYO7A) cause Usher Syndrome 1B (USH1B), a disease characterized by the combination of sensorineural hearing loss and visual impairment termed retinitis pigmentosa (RP). Although the shaker-1 mouse model of USH1B exists, only minor defects in the retina have been observed during its lifespan. Previous studies of the zebrafish mariner mutant, which also carries a mutation in myo7aa, revealed balance and hearing defects in the mutants but the retinal phenotype has not been described. We found elevated cell death in the outer nuclear layer (ONL) of myo7aa(-/-) mutants. While myo7aa(-/-) mutants retained visual behaviors in the optokinetic reflex (OKR) assay, electroretinogram (ERG) recordings revealed a significant decrease in both a- and b-wave amplitudes in mutant animals, but not a change in ERG threshold sensitivity. Immunohistochemistry showed mislocalization of rod and blue cone opsins and reduced expression of rod-specific markers in the myo7aa(-/-) ONL, providing further evidence that the photoreceptor degeneration observed represents the initial stages of the RP. Further, constant light exposure resulted in widespread photoreceptor degeneration and the appearance of large holes in the retinal pigment epithelium (RPE). No differences were observed in the retinomotor movements of the photoreceptors or in melanosome migration within the RPE, suggesting that myo7aa(-/-) does not function in these processes in teleosts. These results indicate that the zebrafish myo7aa(-/-) mutant is a useful animal model for the RP seen in humans with USH1B.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping