Nature Medicine | Spoonful of Medicine

New model organism could be the cat’s meow for studying human disease

transgeniccat91111.jpgThe transgenic cat is out of the bag. Researchers have genetically engineered domestic cats, which should improve scientists’ ability to use felines to study genetic conditions relevant to human disease. The transgenic cats, reported today in Nature Methods, express a gene that encodes a HIV-fighting protein along with a reporter gene, and both genes were transmitted to the cats’ kittens through the germline.

Cats (Felis catus) are far from being the first mammal that preserves engineered genes in their reproductive line. Mice, rats, dogs, pigs, monkeys — all have had transgenes integrated into their DNA that gets successfully passed to down to their offspring. But rodents are fairly dissimilar from humans, whereas monkeys are expensive — not to mention rife with ethical concerns. Cats, researchers say, split the difference, and hold certain advantages over other domesticated animals, including their small size, rapid reproduction, and relative ease-of-care. Indeed, cats have proven to be valuable model organisms for numerous areas of biomedical research, particularly in the fields of neuroscience, behavioral biology, reproductive physiology and endocrinology.

To create the glowing cats, a team led by immunologist Eric Poeschla of the Mayo Clinic in Rochester, Minnesota built lentivirus vectors expressing genes for green fluorescent protein (GFP), and injected the constructs into eggs harvested from discarded ovaries from spayed cats. After injection, the researchers inseminated the eggs with normal sperm and then implanted around fifty fertilized eggs into each of 22 surrogate mothers. Although only three living kittens survived the five successful pregnancies, all of them expressed GFP throughout their skin, as did 7 of 8 fetuses that were aborted prematurely. What’s more, when the transgenic cats were bred to one another, their own kittens also glowed green under a black light.

“Almost all of our pregnancies were transgenic, and that efficiency is important so you don’t have to extensively screen these large animals,” Poeschla told Nature Medicine. “The really great thing is that the animals were healthy and fertile and their kittens were healthy.”

In addition to the reporter gene, the group also inserted a gene called TRIMCyp, which encodes an HIV-targeting restriction factor, into their vector. TRIMCyp, which was discovered in owl monkeys in 2004, is currently under investigation as a potential gene therapy technique in people. This gene was expressed throughout the cats’ bodies, but the researchers have yet to challenge the animals with feline immunodeficiency virus (FIV), the cat version of HIV.

Using this cat model to study FIV — and HIV by extension — “is potentially a valuable application,” wrote developmental biologists Helen Sang and Bruce Whitelaw of the Roslin Institute at the University of Edinburgh in a press statement. “But the uses of genetically modified cats as models for human diseases are likely to be limited and only justified if other models, for example in more commonly used laboratory animals, like mice and rats, are not suitable.”

Beyond the biomedical applications, just one look at the adorable radiant kittens raises the obvious question: where can I get my own glowing cat? Unfortunately, I can’t, says Poeschla: “We’re not interested in frivolous applications.”

Image: courtesy of Eric Poeschla


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