EMBARGOED FOR RELEASE 5 P.M., EST, THURSDAY, JUNE 18, 1998
MELLOW MICE STAND TO BE SOLDIERS IN WAR ON ANXIETY DISORDERS
EAST LANSING, Mich. - Genetic engineering by an MSU scientist to build a better mouse - or at least a mellower mouse - gives scientists a better understanding of the mechanisms of coping with stress and anxiety.
George W. Smith, assistant professor of animal science, and his colleagues at the Salk Institute and Scripps Institute in La Jolla, Calif., bred these mellow mice. Through genetic engineering, a key gene that triggers anxiety was knocked out of their genetic make-up. The impact: Mice with a mellow gene pool. This breakthrough stands to enhance drug research aimed at combating anxiety- and stress-related disorders in humans and animals.
Smith's work is published in the June issue of Neuron.
Reaction to stress - in animals and in humans - can be tracked at the genetic level. One of two corticotropin-releasing factor receptors - known as CRFR1 - mediates the response to stress in the central nervous system. The mice in Smith's research project were genetically engineered so they lack the gene that produces CRFR1. The genetic tinkering took place in the early embryo.
Without CRFR1, the stress response doesn't occur normally. Smith likens the role of CRFR1 to a key that unlocks the cell's response to stress. No CRFR1, no anxiety. The difference in the behavior of the knock out mice is astonishing, Smith said. A regular mouse placed in a brightly lit clear tube acts insecure and stressed. A CRFR1 knock out mouse in the same situation, however, feels secure and relaxed enough to explore his surroundings.
"These mice are mellow," Smith said. "They don't get excited about anything."
There isn't a new breed of mellow mice on the horizon, however. The gene that Smith and colleagues altered controls not only anxiety, but also neuroendocrine development. The adrenal glands of the transgenic mice do not develop normally. As a result, their offspring die soon after birth, due to a condition similar to the respiratory distress syndrome that commonly affects infants born prematurely.
This genetically engineered mouse gives scientists a clear model to study factors that affect anxiety and the stress response, and ultimately to develop new treatments and medications.
"Knock out mice are a valuable tool to tell how the body works," Smith said. "Hundreds of lines of knock out mice, each carrying a deletion of a single gene, have been generated by scientists in recent years, resulting in an explosion of information important to the biomedical community. Information obtained from knock out mice will help form the basis for many of the remarkable advances in treatment of genetic disease, cancer and neurological disorders awaiting us in the future."
In addition to human research applications, Smith said the CRFR1 knock out mice may also prove to be an important model for studying stress-associated disorders, such as shipping fever, which have serious consequences for food-producing animals.
The research was funded by the National Institutes of Health. It was made possible through a team effort with several investigators in the laboratories of Wylie Vale and Kuo-Fen Lee at the Salk Institute and George Koob of the Scripps Institute.
Contact: George W. Smith, (517) 432-5401
or Tom Oswald, (517) 355-2281
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