Fishing for Answers

By Medical Discovery News

Dec. 8, 2012


The stereotypical picture of a scientist includes a white lab coat and a laboratory full of petri dishes, beakers, and test tubes. However, some research questions can only be answered using the complexity of living, breathing multicellular organisms. In these cases, preliminary studies use animal models, and if successful, the final stages of development for a new drug or therapy are conducted using human subjects.

Today, scientists are using a certain animal more extensively in order to understand human disease. The Zebrafish is a small torpedo-shaped fish native to the Indian subcontinent. It’s named for its distinctive horizontal striping pattern of alternating gold or silver and blues stripes.

While it looks nothing like a human, this fish is actually a great model for studying aspects of human disease. Its genome has been completely sequenced, it matures quickly, its genes can be manipulated, and its embryos are transparent. These characteristics make the Zebrafish a highly used and valuable model for genetic and developmental studies.

Two recent reports illustrate the usefulness of the Zebrafish. In one study, scientists examined the role of a human gene called SETDB1 on the progression of a human cancer called melanoma, an aggressive and deadly skin cancer that is responsible for almost 9,000 deaths in the U.S. each year.

Scientists introduced a copy of the SETDB1 gene into Zebrafish embryos, which grew to carry the gene in cells called melanocytes. Then, SETDB1 genes methylated proteins in chromatin, a process that prevents other genes from activating and functioning correctly.

By doing so, SETDB1 accelerates the growth and spread of melanoma. Scientists think that SETDB1 works the same way in humans, so future trials will target this gene and hopefully limit the development of melanoma.

In the second study, a group of scientists used Zebrafish to study human genes thought to contribute to the genetic basis of Autism Spectrum Disorders. While fish aren’t autistic, the scientists aimed to identify the specific genes involved so future therapies could control those genes and therefore the disorder.

The research focused on about 24 genes in a specific genetic region known as 19p11.2 that are known to be missing or duplicated in some autistic patients. One at a time, scientists deleted these genes in Zebrafish embryos and examined the brain abnormalities that resulted, such as changes in the anatomy of brain tissue and the structure of axons that provide the wiring to transmit signals to brain cells called neurons.

Next, they reduced the genes’ production of proteins by 50 percent, which is more like what happens in humans. Two genes continued to lead to abnormal Zebrafish brain development, giving researchers two new targets for treatments that could help those with autism.

So a lowly fish from halfway across the world now plays an irreplaceable role in understanding and treating human disease.

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