The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment

PLoS Genetics
Will YaroshTaosheng Huang

Abstract

Mutations in optic atrophy 1 (OPA1), a nuclear gene encoding a mitochondrial protein, is the most common cause for autosomal dominant optic atrophy (DOA). The condition is characterized by gradual loss of vision, color vision defects, and temporal optic pallor. To understand the molecular mechanism by which OPA1 mutations cause optic atrophy and to facilitate the development of an effective therapeutic agent for optic atrophies, we analyzed phenotypes in the developing and adult Drosophila eyes produced by mutant dOpa1 (CG8479), a Drosophila ortholog of human OPA1. Heterozygous mutation of dOpa1 by a P-element or transposon insertions causes no discernable eye phenotype, whereas the homozygous mutation results in embryonic lethality. Using powerful Drosophila genetic techniques, we created eye-specific somatic clones. The somatic homozygous mutation of dOpa1 in the eyes caused rough (mispatterning) and glossy (decreased lens and pigment deposition) eye phenotypes in adult flies; this phenotype was reversible by precise excision of the inserted P-element. Furthermore, we show the rough eye phenotype is caused by the loss of hexagonal lattice cells in developing eyes, suggesting an increase in lattice cell apoptosis. In adult fli...Continue Reading

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Datasets Mentioned

BETA
AAF58275

Methods Mentioned

BETA
GTPase
scanning electron microscopy
PCR
confocal microscopy
dissection
transgenic
electron
electron tomography
scanning electronic microscopy
dissecting

Software Mentioned

jImage
MUSCLE
BLAST
LSM

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Apoptosis

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