Scientists have genetically modified cats by infecting their eggs with a virus containing a foreign gene—the first time this method has worked in a carnivore. Experts say the advance could make the cat a valuable new genetic model—and potentially protect it from an HIV-like virus.
There are two AIDS epidemics in the world: one in humans, the other in cats. Whereas we can become infected with the human immunodeficiency virus (HIV), cats fall victim to the feline immunodeficiency virus (FIV), which causes nearly identical symptoms. The viruses, known as lentiviruses, are different enough that cats can't catch HIV and people can't get FIV, but most of their basic biochemistry is the same.
Previous studies have suggested that a protein called TRIMCyp is what keeps humans and monkeys from being infected with FIV. The protein, which cats lack, is thought to recognize the virus's outer shell and target it to be degraded.
Eric Poeschla, a molecular virologist at the Mayo Clinic in Rochester, Minnesota, wanted to figure out if giving cats the TRIMCyp gene would make them immune to FIV. But the only proven way of getting a new gene into a cat, somatic cell nuclear transfer, is tricky. The technique, which produced the famous sheep Dolly, involves replacing the nucleus of an egg cell with a nucleus from an adult cell that contains new genes, then implanting the egg into a female. The strategy works in only a fraction of cases. In cats it's been used to create glowing kittens with no other traits, just proof that it can be made to work.
Poeschla and his colleagues turned to a different method—using a virus to carry genes into an egg cell—that had worked in animals including mice and cows but never been successful in a carnivore. Because cells are readily infected by lentiviruses, the researchers made a lentivirus containing the TRIMCyp gene as well as a gene that encodes for a fluorescent protein. The latter allowed them to easily visualize which cells contained the new genetic material—cats with the gene glow green (see picture). After allowing the virus to infect the eggs, the team fertilized them with normal cat sperm and injected them into the fallopian tubes of 22 female cats. Each cat received 30 to 50 eggs.
Five cats became pregnant, with 11 embryos between them, the team reports online today in Nature Methods. Ten of the embryos contained the new genes, and five gave rise to kittens, three of which are still alive. (One kitten was stillborn and another died during birth.) The 23% success rate is much higher than the typical 3% seen with somatic cell nuclear transfer, Poeschla says. As well as a high number of animals per pregnancy, the number of transgenic animals per embryo is also high. "A big advantage is efficiency. Almost all of the offspring are transgenic [carry the new gene], so you're not screening hundreds of animals to find the transgenic ones."
The method's efficiency is only half the story, however. When the researchers tried to infect blood cells from the genetically modified kittens with FIV, the virus didn't replicate well. Poeschla and colleagues next plan to test whether the cats are resistant to FIV, or, if not, whether they are less likely to develop feline AIDS after infection.
Researchers can use the same method to test whether other antiviral proteins from humans and monkeys affect the transmission of FIV, says veterinarian Susan VandeWoude of Colorado State University in Fort Collins. The advance also makes it easier to use cats as model organisms for other biological questions, she says. For example, the visual cortex of a cat's brain is a better model for humans than the visual cortex from mice is. With an easier way to modify genes related to vision, researchers may be able to gain an even higher understanding of how this part of the brain works.
"I think cats will become easier to utilize as a model organism now that you can manipulate the genome," VandeWoude says. "They're not going to replace mice, but it gives another tool to scientists."