Using genetic engineering techniques, researchers at the School of Medicine have developed the first "knock-out" mouse model for a gene that causes breast cancer when it is defective.
The genetically altered mouse will provide important new information about how breast cancer starts, the scientists say. A report on the experiments appeared in the journal Nature Genetics.
Authors of the report are genetics graduate student Lori Gowen; Beverly Koller, research assistant professor of medicine; Kathleen Sulik, professor of cell biology and anatomy; and laboratory technicians Lee Johnson and Anne Latour.
Two genes that, when mutated, can lead to breast cancer have been identified and cloned in the past two years, Gowen said. Little else is understood about such tumor suppressor genes.
"About 5 percent of all breast cancer is hereditary, meaning that it runs in families, and about half of those cases are due to mutations in the BRCA-1 gene," she said. "Virtually nothing is known about the function of this gene, however, except that when it is defective, breast cancer can get started."
Through "gene targeting," scientists deleted the breast cancer gene's DNA from mouse cells, replaced the newly defective genetic material in mouse embryos and transplanted them into foster mother mice. The artificially created mutation then was passed down through otherwise normal mice from one generation to another.
"In this way, a mouse line was created carrying a mutation similar to that which in humans predisposes one to breast cancer," Koller said. "These mice are too young for us to know whether the change will result in tumors, but if this is the case, they will provide an important tool for studying and testing therapies to intervene in this devastating disease."
The National Heart, Lung and Blood Institute and the National Institute of Alcohol Abuse and Alcoholism supported the research.
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