NIH Research Matters
September 14, 2009
Monkey DNA Swap May Block Mitochondrial Disease
A new technique for exchanging DNA between egg cells has led to the birth of 4 healthy monkeys, scientists report. The method may one day provide new options for preventing certain inherited disorders that pass from mother to child in mitochondria, the tiny capsule-shaped structures that create energy inside nearly all the body's cells.
Most of our DNA is in the cell's nucleus. This DNA contains a mixture of genetic material from both parents. Each cell's mitochondria also contain small pieces of DNA, called mitochondrial DNA (mtDNA). This genetic material is inherited only from the mother, because mitochondria pass from mother to offspring in the fluid, or cytoplasm, of the mother's egg.
Defects in mtDNA cause several rare and deadly disorders, such as mitochondrial myopathies and Leigh's disease. They've also been linked to more common conditions, including diabetes, cancer and neurodegenerative disorders like Alzheimer's disease.
Earlier efforts to correct mitochondrial disorders have proven frustrating. Adding healthy mtDNA into eggs doesn't overcome the problems caused by the remaining faulty mtDNA. And researchers who tried removing nuclei from defective eggs and transplanting them into eggs with healthy mtDNA found that the procedure was inefficient and plagued by contamination with abnormal mtDNA.
In the new study, Dr. Shoukhrat Mitalipov and his colleagues at the Oregon Health and Science University developed a way to safely remove nuclear DNA from monkey egg cells without bringing along any mtDNA . Key to their success was a method they'd devised 2 years earlier to remove nuclear DNA during a stage of the egg's cell cycle called metaphase II. At this stage, the nuclear membrane has broken down and the cell's DNA is condensed into tightly packed chromosomes attached to a protein structure called a spindle. Their work was supported in part by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Center for Research Resources (NCRR).
As reported in the online edition of Nature on August 26, 2009, the scientists used advanced microscopy to guide the safe and precise removal of spindle-chromosomal complexes from monkey egg cells. The complexes were then inserted into recipient egg cells that had their nuclei removed. The resulting eggs were fertilized with sperm, and 15 embryos were implanted into 9 female monkeys. Three gave birth to 4 healthy offspring, including a set of twins.
Analysis of the infant monkeys' cells showed that they had mtDNA from 1 female and nuclear DNA from another. No mtDNA from the original egg—the source of the nuclear DNA—could be detected. The researchers also found no evidence of chromosome damage from the procedure. This finding raises the possibility of preventing damaged mtDNA from passing onto offspring. However, extensive safety studies would first need to be completed.
"Pending further research, the findings hold the potential of allowing a couple to have a child who is biologically their own, but is free of any conditions associated with defects in maternal mitochondria," says NICHD Director Dr. Duane Alexander.
- Embryonic Stem Cell Milestone Achieved in Primates:
- Mitochondrial DNA:
- Mitochondrial Myopathies:
- Leigh's Disease:
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