Cloning a cow impervious to mad cow disease

BLACKSBURG, Virginia, January 8, 2004 (ENS): The scientist who cloned Dolly, the world's first cloned sheep, is now working to clone cattle that are genetically incapable of developing mad cow disease.
As government officials try to limit the economic and health risks related to the nation's first case of bovine spongiform encephalopathy (BSE), or mad cow disease, found in December 2003, researchers in the Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM) at Virginia Tech are attempting to genetically engineer their way to a BSE free cow.

Associate professor Will Eyestone, who heads the VMRCVM's transgenic animal research program, is the molecular reproductive biologist who was senior research scientist for PPL Therapeutics, the organization that cloned Dolly.

Together with Bill Huckle, associate professor of biomedical science, Eyestone is using the same somatic cell transfer technology that PPL used to create Dolly and Mr. Jefferson, the first cloned calf to to clone a cow without normal prions.

Transmissible spongiform encephalopathies such as mad cow disease and its human counterpart, variant Creutzfeldt-Jakob disease, are not caused by bacteria or viruses. The causative agent is prions, proteins that are a normal part of the animal's nervous system. But prions can mutate to abnormal forms, and these fatal brain-wasting diseases are the result.

If efforts to produce a normally functioning cow that lacks the genetic ability to code for the production of prions are successful, the researchers may have found a strategy for eliminating mad cow and related diseases.

"In order to be susceptible to prion disease, the individual has to be able to express the prion," says Eyestone. "We know that this prion does not appear to be required for normal functions of life."

We know that if you knock out these prion proteins in laboratory mice that there is no apparent negative effect, Eyestone explained. "But the mouse has not been that informative to us and we are hoping that the cow will be more so."

This research is funded by the National Institutes of Health. The goal of the NIH grant is to engineer a cow that is genetically incapable of producing prions, and then determine whether the animal is impaired by the lack of the prion.

Eyestone expects the cow to be cloned later this year.

While the prospects of "cloning" prion free cattle on the scale of America's 100 million head cattle herd may seen daunting, Eyestone points out that with the widespread use of artificial insemination in modern agriculture, great strides could be made in as few as six generations.

On a smaller scale, Eyestone envisions sub-populations of prion free cattle that are produced to make pharmaceutical compounds for human use, eliminating the risk that a drug produced to promote human health might in fact cause a fatal transmissible spongiform disease.

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