Zebrafish to shed light on human mitochondria...(study have not been assessable in mice. ...)

Baden, a veterinarian, performed several experiments, using RNA-blocking reagents known as morpholinos to reduce gene expression of both a critical COX subunit and Surf1, an assembly-factor protein that when mutated can lead to Leigh syndrome, a severe neurological disorder. She targeted a variety of proteins, alone and in combination, and then added back components to rescue each deficiency. Normal COX activity declined as much as 50 percent in the experimental conditions and resulted in developmental defects in endodermal tissue, cardiac function and swimming behavior in the zebrafish.

"The unique characteristics of zebrafish make them an ideal model for studying the effects of mitochondrial deficiencies on early development," said Baden, who earned her doctorate in July and is now the veterinarian at the UO-based Zebrafish International Resource Center. "Because they develop outside of a uterus and are transparent in early stages, I was able to visualize the effects that molecular alterations have on cell biology, nervous system development, cardiac function and fish behavior."

The external and transparent embryo, Guillemin said, will allow scientists to create specific deficits that mirror those in humans. "The transparency of the embryo will let us see primary defects, what happens in the earliest stages, rather than having to settle for seeing secondary downstream defects later in the disease state," she said.

"Different tissues respond differently to specific losses in mitochondria."

Baden and Guillemin said that the use of zebrafish will improve scientific understanding of the mechanisms of mitochondrial associated pathology in people and speed the identification of new treatments for mitochondrial diseases.

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