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Fishing for answers

by Ruth SoRelle, MPH

Zebrafish

Why would the National Institutes of Health build a $10 million, 5,000-square foot facility to house more than 500,000 fish in 25,000 tanks?

Most people would shrug their shoulders and be relieved that it’s not more. Those in the few and sophisticated laboratories that study zebrafish (also known as Danio rerio) understand. The fish is rich in features that make it ideal for studying genetics and development. Yet, the numbers of laboratories in Houston specializing in research on these water creatures are fewer than the fingers on one hand.

No more than three centimeters long, slender and sporting dark stripes, zebrafish are native to Southeast Asia. In captivity, they live on brine shrimp and algae. Their lifespans are approximately five years and they become adults within three months of hatching. Eggs are fertilized externally, and on average, a fish lays 200 eggs at once.

The genome is approximately 1,700 megabases and has 25 diploid chromosomes. A preliminary genome sequence has been released and is now being refined.

The zebrafish probably first entered the laboratory in the late 1960s, and by the mid-1970s, techniques that allowed the generation of fish who had two of the same gene (homozygous) were developed. In 1982, George Streisinger, PhD, at the University of Oregon and considered the “father” of laboratory study of zebrafish, actually cloned one – the first time a vertebrate had been cloned.

Mary Ellen Lane, PhD, an assistant professor at Rice University and an adjunct faculty member in developmental biology at Baylor College of Medicine in Houston, works with zebrafish in her laboratory and said, “It’s a very good genetic model. In some ways, it’s superior to mammalian systems.”

Zebrafish -- courtesy of Mary Ellen Lane

Using radiation and chemicals, scientists can cause mutations in the fish. They can locate the mutated fish based on their actions and the way they look.

“Those kinds of screens have been done on a large scale, and they are successful in identifying a number of genes that affect biological processes,” she said. In fact, she said, she does not need to generate her own mutant fish. She can obtain the mutants she needs from those that have already been generated.

Many new methods of generating fish with specific mutations are under investigation. In one, scientists use a chemical to cause mutations and then look for the specific change in the gene using a technique called PCR.

The fish embryos are transparent. Using green fluorescent protein that spontaneously generates a green light, scientists can mark specific cells in an embryo and actually follow development of organs as they occur.

“We are studying eye development in my laboratory,” said Lane. “We can actually start our monitoring before there is a retina and watch its genesis. We can watch the eye develop from the brain at early stages that are not accessible in the mouse.”

Such techniques are key to understanding the processes of life. Using model organisms such as the zebrafish make such work possible.

(Editor’s Note: This is the third in an occasional series of articles spotlighting the organisms important in a variety of biological studies. Drosophila melanogaster, the fruit fly, was first to be featured and Caenorhabditis elegans, a nematode, was the second).

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