The power of animal models  pg. 2

One of today’s up-and-coming animal models is the tiny zebrafish, Danio rerio. Its embryo is transparent and develops rapidly: within 24 hours of fertilization, it has a beating heart.

Lilianna Solnica-Krezel, Ph.D., and her colleagues at Vanderbilt University have helped establish the importance of prostaglandin and bone morphogenetic protein (BMP) signaling pathways in zebrafish development.

Prostaglandins are fat-derived compounds that in humans have been linked to pain, inflammation and cancer. BMPs induce formation of bone and cartilage, but disruption of BMP signaling also can affect development of the body plan.

While mice and rats remain important in early drug development and testing, scientists have begun to use zebrafish embryos in screens for new compounds with drug-like activity.

In a recent “chemical genetics” study, Charles Hong, M.D., Ph.D., and his colleagues at Harvard Medical School exposed developing zebrafish to thousands of chemicals to see which might disrupt the dorsoventral (back-to-front) body pattern.

One compound, which they called “dorsomorphin,” turned out to be the first selective inhibitor of BMP signaling to be discovered.

In mice, inhibiting BMP signaling increases iron levels in the blood, suggesting that dorsomorphin might be useful in treating forms of anemia.

“This work demonstrates the power of chemical genetics,” says Hong, currently a Vanderbilt faculty member in Cardiovascular Medicine. .


Gary Kuhlmann, a freelance science writer based in Elgin, S.C., contributed to this story.

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