Suppression of complex I gene expression induces optic neuropathy
- 23 January 2003
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 53 (2) , 198-205
- https://doi.org/10.1002/ana.10426
Abstract
Optic nerve degeneration is a feature common to diseases with mutations in genes that encode complex I of the respiratory chain. Vulnerability of this central nervous system tract is a mystery, because of the paucity of animal models used to investigate effects of the mutated DNA in tissues rather than isolated in cultured cells. Using a ribozyme designed to degrade the mRNA encoding a critical nuclear‐encoded subunit gene of complex I (NDUFA1), we tested whether oxidative phosphorylation deficiency can recapitulate the optic neuropathy of mitochondrial disease. Injection of adenoassociated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy. Ann Neurol 2003Keywords
This publication has 29 references indexed in Scilit:
- Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathiesNeurochemistry International, 2002
- Mitochondrial genetics and diseaseTrends in Biochemical Sciences, 2000
- Resolution of the Membrane Domain of Bovine Complex I into Subcomplexes: Implications for the Structural Organization of the EnzymeBiochemistry, 2000
- Mitochondrial oxidative stress in mice lacking the glutathione peroxidase-1 geneFree Radical Biology & Medicine, 2000
- Mitochondrial Diseases in Man and MouseScience, 1999
- A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocatorNature Genetics, 1997
- Tissue-specific selection for different mtDNA genotypes in heteroplasmic miceNature Genetics, 1997
- Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNANature Genetics, 1996
- Protein Sorting to Mitochondria: Evolutionary Conservations of Folding and AssemblyScience, 1990
- Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic NeuropathyScience, 1988