UW researchers are using zebrafish, popular aquarium fish sold under the trade name zebra danios, to screen for genes or chemical compounds that make the fish either resistant to or susceptible to hearing loss caused by certain antibiotics and chemotherapeutic compounds.

The researchers have divided the zebrafish into several tanks. There are two facilities and roughly 1,500 tanks, with more than 500 families of fish shared by several labs.

Each tank has fish containing different genotypes, or genetic makeups, that carry random sets of mutations. These families are screened for how they respond to certain ototoxic drugs, which cause damage to hair cells in ears.

They look for two kinds of genes, said David Raible, a UW professor of biological structure. Genes that increase susceptibility and mutations that are resistant at a normal dose are sought after, he said.

“[We are] beginning to identify what [these genes] are,” Raible said. “Some are new, [and] people haven’t studied [them] before but know that there are human counterparts. The next step is to see what these genes are doing.”

Certain therapeutic drugs, including antibiotics and chemotherapeutic compounds such as aminoglycoside antibiotics or cisplatin that are used to treat testicular cancer, can cause irreversible hearing loss or balance disorders, Raible said.

Zebrafish are advantageous because they produce a lot of offspring and respond the same ways as humans to these drugs.

This allows researchers to see how certain families will react to the drugs and hopefully find molecules that contribute to hair cell death.

The loss of hair cells is one of the main causes of hearing loss and balance disorders, Raible said. This is partially attributed to variations in genetic factors and environmental susceptibility, which may be dependent on genetic makeup.

Zebrafish have stripes of mechanosensory hair cells, similar to those found in the mammalian inner ear on the lateral line system, that allow them to sense vibrations or changes in the environment.

“Fish hair cells will take up a dye, making them easy to see,” Raible said. “So when you add neomycin [an antibiotic that damages the hair cells], hair cells die, and the dye goes away.”

These hair cells are also sensitive to certain agents that cause hearing loss in humans.

Raible and Edwin Rubel, a professor in the departments of otolaryngology, physiology and biophysics, formed a collaboration between their labs and developed a technique that allows them to quickly screen many animals and potential molecules that may help protect against hearing loss and balance disorders.

The zebrafish are placed in spawning cages containing small holes at the bottom to filter out the eggs; otherwise the fish would eat the eggs.

“Zebrafish produce hundreds of eggs,” Raible said. “We can keep them in families and follow pedigrees.”

[Reach reporter Doris Wu at news@thedaily.washington.edu.]