WASHINGTON (AP)--In a study that could help develop cattle bred to resist Bovine Spongiform Encephalopathy, researchers showed in a laboratory experiment a mutated protein may protect animals from the prion protein that causes the brain-destroying disorder.
Researchers at the University of California, San Francisco, reported they genetically altered a strain of mice so the animals made a mutated form of prions which then prevented the animals from becoming ill when injected with a form of prion that usually causes the brain disease.
"We found that the (genetically engineered) mouse became completely resistant to the prion disease," said Dr. Jiri G. Safar, a co-author of the study appearing this week in the Proceedings of the National Academy of Sciences.
Safar said he and his colleagues now hope to develop a genetically engineered strain of cattle which is resistant to BSE.
Patrick W. Dunne, a veterinary scientist at Texas A&M and a BSE researcher, called the study by Safar and his colleagues "a breakthrough."
"This means that prion diseases in livestock could be at least inhibited, if not eliminated," said Dunne. "It is a very significant finding."
Prion diseases include BSE in cattle, scrapie in sheep and Creutzfeldt-Jakob Disease in humans. There is also a related wasting disease in deer and elk. The diseases are caused by an abnormal form of the prion protein that makes the normal form of prion change its shape and become infectious. The abnormal prion causes the progressive, irreversible destruction of brain cells. The disease is fatal in all species where it occurs.
An epidemic of BSE developed in Britain in the 1990s after cattle there were given feed that included body parts from sheep with scrapie. Researchers later found that some people developed a form of prion disease, called new variant-Crutchfeld-Jacob Disease, after eating meat from infected cattle. The discovery caused a temporary ban on the import of British beef in many countries and the destruction of thousands of cattle in the United Kingdom.
More than 100 people in Europe have been diagnosed with new variant-CJD, but that form of prion disease has not been diagnosed in the United States. A type of CJD not related to eating meat, however, does occur in the United States.
In the new study, Safar and his co-authors, which includes Stanley B. Prusiner, who was awarded a Nobel Prize for discovering prion disease, found by altering the genes of mice they could make the animals resistant to the brain-destroying disease.
Safar said earlier studies in Japan and elsewhere had suggested that some mutated forms of prion prevented the disease-causing form of the protein from causing disease.
To test this idea, researchers engineered a mouse strain with genes that caused key changes in the amino acids that make up the prion protein. When mature, the mice were injected with high doses of the disease-causing form of prion.
Although some of the test animals did form some pathogenic prions, none of them developed the full blown prion disease. Safar called this the "silent expression" of the diseased prion.
In contrast, mice with the normal type of prion developed a fatal brain disorder when they were injected with the disease-causing form of prion.
With selective genetic engineering, Safar said, "it is possible we could wipe out even the silent expression and transmission of the pathogenic prion."
Safar said that altering the prion gene to make it resistant to the disease is better than eliminating the gene altogether, as some have suggested. Taking out the gene altogether, he said, could cause subtle health changes in the animals since normal prions play a role in brain cell maintenance.