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Transparent zebrafish set to aid cancer studies

By Wai Lang Chu, 13-Feb-2008

Related topics: Processing

Researchers have created a transparent adult zebrafish that will allow scientists to observe disease processes in a laboratory environment and may explain the cancer life cycle and why its cells migrate to other parts of the body.

The new fish is a potential breakthrough in laboratory research as current zebrafish are transparent as embryos but turn opaque as adults. This breed of fish can now be used to observe complex mechanisms such as tumour metastasis all in real time.

 

 

 

Whether or not a cancer is local or has spread to other locations affects treatment and survival and this is the biggest problem that oncologists face. If the cancer spreads to other tissues and organs, it may decrease a patient's likelihood of survival.

 

 

 

"The classic method for studying human diseases in animals is to allow the animal to get the disease, kill and dissect the animal, then ask, 'what happened?'" said Richard White, a clinical fellow in the Stem Cell Program at Children's Hospital in Boston.

 

 

 

"But in cancer and other fast-changing processes that traverse the body, this method is bound to miss something. It's like taking a photograph when you need a video," he added.

 

 

 

Zebrafish are genetically similar to humans and are good models for human disease. By creating a fluorescent melanoma tumour in the transparent fish's abdominal cavity White was able to view cancer cell spread under a microscope within five days.

 

 

 

The transparency allowed White to see individual cells metastasise, something that has not been previously possible, in real-time within a living organism.

 

 

 

White observed the melanoma cells seemed to know where to go, travelling directly to the skin after leaving the abdominal cavity. The process was not a random occurrence.

 

 

 

White said he planned to study tumour cell homing, then look for ways to modify the tumour cells or cells of the host so that the spreading cells never find their new location.

 

 

 

Zebrafish have proved a versatile and adaptable organism ideally suited as a laboratory subject. Zebrafish embryos develop rapidly, progressing from eggs to larvae in less than three days.

 

 

 

The embryos are large, robust, and transparent and develop externally to the mother, characteristics which all facilitate experimental manipulation and observation. Their nearly constant size during early development facilitates simple staining techniques, and drugs may be administered by adding directly to the tank.

 

 

 

White created the transparent fish by combining two existing zebrafish breeds. Zebrafish have three pigments in their skin - reflective, black, and yellow. White mated a breed that lacks reflective pigment, with one that lacks black pigment. The offspring had only yellow pigment in their skin, essentially looking clear.

 

 

 

The fish's brain, heart, and digestive tract are also visible, allowing researchers to study genetic defects of these organs from early embryonic development through adulthood.

 

 

 

"What happens in a living organism is different than what happens in a dish," White stated. He hopes this tool will provide insight into how mutated genes cause diseases ranging from Alzheimer's disease to inflammatory bowel disease.