Glowing transgenic cats could boost AIDS research

Three cats genetically modified to resist feline immunodeficiency virus (FIV) have opened up new avenues for AIDS research.

Green glow the cats

The research could also help veterinarians combat the virus, which kills millions of feral cats each year and also infects big cats, including lions.

Prosaically named TgCat1, TgCat2 and TgCat3, the GM cats – now a year old – glow ghostly green under ultraviolet light because they have been given thegreen fluorescent protein (GFP) gene originating from jellyfish.

The GM cats also carry an extra monkey gene, called TRIMCyp, which protects rhesus macaques from infection by feline immunodeficiency virus or FIV – responsible for cat AIDS.

By giving the gene to the cats, the team hopes to offer the animals protection from FIV. Their study could help researchers develop and test similar approaches to protecting humans from infection with HIV.

Cat immunity

Already, the researchers have demonstrated that lab cultures of white blood cells from the cats are protected from FIV, and they hope to give the virus to the cats to check whether they are immune to it.

"The animals clearly have the protective gene expressed in all their tissues including the lymph nodes, thymus and spleen," says Eric Poeschla of the Mayo Clinic College of Medicine in Rochester, Minnesota, who led the research. "That's crucial because that's where the disease really happens, and where you see destruction of T-cells targeted by HIV in humans."

The animals are not the first GM cats, but the new method is far more efficient and versatile than previous techniques. The first cloned cat, born in 2001, was the only one to survive from 200 embryos, each created by taking an ear cell from cats, removing the nucleus and fusing it with a cat egg cell emptied of its own nucleus.

Poeschla's technique is far more direct, far more efficient and far simpler, and has already been used successfully to make GM mice, pigs, cows and monkeys. He loads genes of interest into a lentivirus, which he then introduces directly into a cat oocyte, or egg cell. The oocyte loaded with the new genes is then fertilised and placed in the womb of a foster mother.

From 22 implantations, Poeschla achieved 12 fetuses in five pregnancies, and three live births. And out of the 12 fetuses, 11 successfully incorporated the new genes, demonstrating how efficient the method is.

One surviving male kitten, TgCat1, has already mated with three normal females, siring eight healthy kittens that all carry the implanted genes as well, showing that they are inheritable.

But there are doubts about whether cats will replace monkeys as the staples of HIV research. "It's fantastic they've created GM cats," says Theodora Hatziioannou of the Aaron Diamond AIDS Research Center in New York City.

"But what makes research in monkeys so much better is that SIV in monkeys is much more closely related to HIV, so it's more straightforward to draw conclusions than it would be with FIV.