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 adeno-associated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy.
| Original language | English |
|---|---|
| Pages (from-to) | 198-205 |
| Number of pages | 8 |
| Journal | Annals of Neurology |
| Volume | 53 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Suppression of complex I gene expression induces optic neuropathy. / Qi, Xiaoping; Lewin, Alfred S.; Hauswirth, William W.; Guy, John.
In: Annals of Neurology, Vol. 53, No. 2, 01.02.2003, p. 198-205.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of complex I gene expression induces optic neuropathy
AU - Qi, Xiaoping
AU - Lewin, Alfred S.
AU - Hauswirth, William W.
AU - Guy, John
PY - 2003/2/1
Y1 - 2003/2/1
N2 - 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 adeno-associated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy.
AB - 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 adeno-associated virus expressing this ribozyme led to axonal destruction and demyelination, the hallmarks of Leber hereditary optic neuropathy.
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UR - http://www.scopus.com/inward/citedby.url?scp=0037310673&partnerID=8YFLogxK
U2 - 10.1002/ana.10426
DO - 10.1002/ana.10426
M3 - Article
C2 - 12557286
AN - SCOPUS:0037310673
VL - 53
SP - 198
EP - 205
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 2
ER -