PUBLICATION
Early developmental pathology due to cytochrome c oxidase deficiency is revealed by a new zebrafish model
- Authors
- Baden, K.N., Murray, J., Capaldi, R.A., and Guillemin, K.
- ID
- ZDB-PUB-070907-25
- Date
- 2007
- Source
- The Journal of biological chemistry 282(48): 34839-34849 (Journal)
- Registered Authors
- Guillemin, Karen, Murray, Katy
- Keywords
- none
- MeSH Terms
-
- Acridine Orange/pharmacology
- Time Factors
- Apoptosis
- Heart/embryology
- Heart/physiology
- Cytochrome-c Oxidase Deficiency/genetics*
- Zebrafish
- Electron Transport Complex IV/genetics*
- Electron Transport Complex IV/physiology*
- Humans
- Myocardium/metabolism
- Neural Tube/embryology*
- Immunohistochemistry/methods
- Phenotype
- Gene Expression Regulation, Developmental*
- Motor Neurons/metabolism
- Animals
- DNA, Mitochondrial/metabolism
- PubMed
- 17761683 Full text @ J. Biol. Chem.
Citation
Baden, K.N., Murray, J., Capaldi, R.A., and Guillemin, K. (2007) Early developmental pathology due to cytochrome c oxidase deficiency is revealed by a new zebrafish model. The Journal of biological chemistry. 282(48):34839-34849.
Abstract
Deficiency of cytochrome c oxidase (COX) is associated with significant pathology in humans. However, the consequences for organogenesis and early development are not well understood. We have investigated these issues using a zebrafish model. COX deficiency was induced using morpholinos to reduce expression of CoxVa, a structural subunit, and Surf1, an assembly factor, both of which impaired COX assembly. Reduction of COX activity to 50% resulted in developmental defects in endodermal tissue, cardiac function, and swimming behavior. Cellular investigations revealed different underlying mechanisms. Apoptosis was dramatically increased in the hindbrain and neural tube and secondary motor neurons were absent or abnormal, explaining the motility defect. In contrast, the heart lacked apoptotic cells but showed increasingly poor performance over time, consistent with energy deficiency. The zebrafish model has revealed tissue-specific responses to COX deficiency and holds promise for discovery of new therapies to treat mitochondrial diseases in humans.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping