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
  • Animals
  • Apoptosis
  • Cytochrome-c Oxidase Deficiency/genetics*
  • DNA, Mitochondrial/metabolism
  • Electron Transport Complex IV/genetics*
  • Electron Transport Complex IV/physiology*
  • Gene Expression Regulation, Developmental*
  • Heart/embryology
  • Heart/physiology
  • Humans
  • Immunohistochemistry/methods
  • Motor Neurons/metabolism
  • Myocardium/metabolism
  • Neural Tube/embryology*
  • Phenotype
  • Time Factors
  • Zebrafish
PubMed
17761683 Full text @ J. Biol. Chem.
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
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes