The mice that roared

Oklahoma City, Dec. 3, 2007 – How do complex networks of genes control obesity, cancer and heart disease? The unique rodents of the Oklahoma Medical Research Foundation may hold the answer.

Their small size and short gestation periods make mice ideal models for studying human disease. Although garden-variety rodents don’t make the cut for research, technological advances have made it possible for scientists to design mice with extremely specific genetic mutations.

This fall, the Nobel Prize in medicine was awarded to a trio of scientists who developed a powerful technology that allows scientists to create models of human disease in mice. OMRF is home to more than 20,000 such genetically modified mice, many created using the technology developed by this year’s Nobel laureates.

Using powerful “knock-out” and “knock-in” technologies, which allow scientists to add or delete genes from the rodents, researchers at OMRF have bred dozens of variations of mice, including strains that develop symptoms of Alzheimer’s disease, Huntington’s disease and heart disease. They now are studying these animals in hopes of developing a better understanding—and, ultimately, new treatments—for these illnesses.

“Humans and mice share more than 95 percent of their genes, and the two species form genetic networks that are genetically similar,” said OMRF President Stephen Prescott, M.D. “What is true for the mouse is often true for people, too. For that reason, mice have become the living test tubes of medical research.”

At OMRF, the mice spend their lives, which range from a few months to several years, in the Donald W. Reynolds Center for Genetic Research. To enter the $15 million state-of-the-art “barrier” facility, researchers and technicians must don paper boots, scrubs and caps and undergo a 90-second “air shower,” which removes any bacteria, viruses or other pathogens the scientists might carry into the facility. Even instruments—everything from mouse cages to computers—must undergo a hydrogen peroxide cleansing process before entering the facility.

The sanitation procedures are necessary to protect the fragile creatures that are the key to solving the mysteries of human disease. In addition to playing a pivotal role in the research of Oklahoma scientists, the mice bred at OMRF also are sent to labs in 26 states and 14 foreign countries to help researchers learn more about human illnesses and how they behave in a living creature.

For example, OMRF’s Linda Thompson, Ph.D., spent nearly a decade (and more than $500,000) breeding a strain of mouse that lacked a particular enzyme. She used the animals to understand the enzyme’s role in immune system development, but soon scientists at other institutions began requesting the mice for their own research.

Those researchers have since discovered that Thompson’s rodents are the perfect tools for studying multiple sclerosis, inflammation and a host of other biologic processes. Today, the descendants of Thompson’s original mouse—which she named Hope—travel to labs around the world.

“We send them as far away as Shanghai, Osaka and Melbourne, Australia,” said Thompson. Soon, Brazil will also join that list. “If I were to write a story about Hope,” said the OMRF researcher, “I’d call it The Mouse That Roared.”

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