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Can a zebrafish help solve medical mysteries?

Because zebrafish hearts are so similar to our own, scientists are using the fish to study many aspects of heart disease, particularly the role of genetic mutations that might cause heart abnormalities.

One disease, called familial hypertrophic cardiomyopathy (HCM), is the leading cause of sudden death in young athletes. Researchers discovered that mutations in a gene that codes for a heart protein called troponin T are responsible for 15% of the cases of HCM. But until recently, the way the mutation caused the disease remained a mystery.

Scientists had been studying a collection of mutants that developed heart abnormalities. The most severe was a defect named silent heart ; embryos with this defect had hearts that did not beat at all. Using molecular techniques, researchers found that the gene that, when mutated, produces silent heart also encodes the zebrafish version of the troponin T protein. In the case of silent heart, they found the gene so severely mutated that it failed to make any useful troponin T, and that this affected the production of two other important heart proteins. The failure of this system of proteins created disorganized heart muscle cells (myocytes, see movie ) that in turn failed to organize into a heart effective at circulating blood. In humans with HCM, myocytes are also disorganized, which can lead to an abnormal heartbeat, and in some cases, sudden death.

By examining the effects of the silent heart mutation in zebrafish, more light can be shed on how mutations in the human troponin T could result in HCM in humans. Researchers hope to find still more parallels between zebrafish heart mutants and heart disease in humans. Understanding the genetics and biology behind heart formation and function will help scientists design therapies and interventions in the future to help keep hearts healthy.