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B. D. Perkins, S. C. Lunt, S. Sukumaran, B. Krock; Mutation in the atp6v0C Gene Causes Photoreceptor and RPE Degeneration in the Zebrafish piegus Mutant. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4551. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The retinal pigment epithelium (RPE) plays an essential role in photoreceptor survival and defects in RPE function contribute to some forms of retinal degeneration. The purpose of this study was to characterize the ocular phenotype and identify the causative mutation in the zebrafish piegus (pgu) mutant, which was found to exhibit RPE and photoreceptor degeneration.
Morphological screening was used to identify the pgu mutant. Retinas from wild type and mutant animals were examined between 3-5 days post fertilization (dpf) using standard histological techniques and immunohistochemistry. Ultrastructural defects were identified using transmission electron microscopy. Cell autonomy was examined by generating genetic mosaic animals. We use complementation analysis and direct sequencing to identify the causative mutation in pgu mutants. Injection of morpholino oligonucleotides was done to phenocopy the mutant phenotype.
The pgu mutants exhibited hypopigmentation in the RPE and body. The RPE and photoreceptors also exhibited altered morphology. Cell death was most pronounced near the marginal zone, which is a region of proliferative retinal stem cells. Ultrastructural analysis revealed severely disrupted photoreceptor morphology and abnormal melanosomes. Complementation analysis with several hypopigmentation mutants exhibiting retinal abnormalities found that the hi1207 allele failed to complement pgu, which demonstrated a mutation in the atp6v0c gene is responsible for the pgu phenotype. Injection of morpholinos against the atp6v0c gene reproduced the phenotypes observed in pgu mutants.
Zebrafish pgu mutants exhibit ocular hypopigmentation and retinal degeneration. Mutations in the v-ATPase gene atp6v0c are causative for the phenotypes observed in pgu mutants. The pgu mutants exhibit RPE and photoreceptor dystrophy similar to that observed in human diseases such as retinitis pigmentosa and Hermansky-Pudlak syndrome. The pgu mutants may serve as a useful model to understand the role of the v-ATPase complex in supporting the RPE and photoreceptors.
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