Green mice a coup for Baltimore team

Using specially prepared HIV-derived viruses stripped of their disease-causing potential, Caltech biologist and president David Baltimore and his team have invented a new method of introducing foreign DNA into animals; it could have wide-ranging applications in biotechnology and experimental biology.

The Baltimore team reported on the January 10 Science Express Web site about their study of single-cell mouse embryos that have been virally infected in a manner that leaves a new gene from a jellyfish permanently deposited in their genomes. The mice, after they have been carried to term, have at least one copy of the gene in 80 percent of the cases, and 90 percent show high levels of the jellyfish protein. Further, the study shows that the mice’s offspring inherit the genes and make the new protein. Thus the method makes “transgenic” mice—meaning the new gene has been transferred—with new genetic potential.

According to Baltimore, the use of the HIV-like viruses could prove far superior to the current method of producing transgenic animals by pronuclear injection.

“It’s surprising how well it works,” says Baltimore, whose Nobel Prize–winning research on the genetic mechanisms of viruses 30 years ago is central to the new technique. “This technique is much easier and more efficient than the procedure now commonly in use, and the results suggest that it can be used to generate other transgenic animal species.”

The technique exploits features of lentiviruses, HIV-like viruses made incapable of causing AIDS , to carry new genes into the cell’s existing genome. In this case, newly fertilized mouse eggs were engineered to carry the green fluorescent protein (GFP) derived from jellyfish.

Baltimore and his team developed two ways of introducing the lentivirus into cells: microinjection of the virus under the layer that protects recently fertilized eggs, or incubation of denuded fertilized eggs in a concentrated solution of the virus. The transgenic mice, once they are born, carry a protein marker in all body tissues that make them glow green under a fluorescent light. The trait is a permanent feature of the animal’s genome, and thus is carried throughout life and is inheritable by offspring.

Transgenics holds promise because the techniques can be used to “engineer” new, desirable traits in plants and animals. A transgenic chicken, for example, might produce eggs low in cholesterol. In experimental biology, transgenic animals are valuable in the laboratory for fundamental research. According to Baltimore, the procedure works on rats as well as mice, a huge advantage because of the many applications in which rats are preferable.
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