Scientists working with glow-in-the-dark zebrafish have identified a gene that plays a role in regulating cholesterol metabolism, according to a report published today in the journal Science. The new findings could help lead to better drugs for controlling cholesterol in the future.
Though more distantly related to humans than are other animals such as mice, zebrafish share nearly all of our genes. And they can be extremely useful in some biological studies because the fish are transparent when they are young. With that in mind, Steven Farber of Thomas Jefferson University in Philadelphia and his colleagues engineered special fat molecules called "optical reporters" that glow when broken down by an intestinal enzyme. These molecules, they reasoned, would enable them to observe zebrafish digestion from a biochemical perspective. Next the researchers generated random genetic mutations in the fish by exposing males to a chemical agent and breeding families exhibiting the various mutations. They then fed the optical reporters to the mutant zebrafish embryos, watching the resulting pattern of fluorescence and screening for changes in lipid processing.
Carriers of one mutation in particular, which they dubbed fat free, showed drastically reduced cholesterol and phospholipid processing. (Other experiments illustrated the effects of the cholesterol blocking drug, Lipitor, which prevented the fish from metabolizing the optical reporters, and thus from glowing.) Down the road, the researchers note, optical reporters should identify genes involved in lipid metabolism diseases such as atherosclerosis, as well as other disorders.