Gene Study Of Hibernation May Aid Organ Transplants, Hypothermia

Scientists have long understood why animals hibernate. But how they perform this amazing transformation -- exactly which genes control its onset in autumn and its reversal come spring -- has largely remained a mystery.

Now, thanks to a pioneering five-year study by North Carolina State University geneticists, the pieces of that genetic puzzle are starting to come together.

Dr. Matthew Andrews and his research team have identified and mapped two genes for enzymes that play important roles in hibernation in ground squirrels, and have discovered that these genes are nearly identical to ones found in nonhibernating mammals, including humans.

Because the genes are found in all mammals, not just in species that hibernate, the study's findings have implications far beyond the field of zoology, Andrews says.

"If we can identify the enzymes responsible for preserving organs, reducing glucose consumption and maintaining muscle tone during an extreme state like hibernation, physicians could use that knowledge to develop new strategies for prolonging the 'shelf life' of human organs intended for transplants or for helping humans suffering from starvation, muscle atrophy, hypothermia and hypoxia," he explains.

One of the genes identified by Andrews and his research team controls the production of pancreatic triglyceride lipase (PL), an enzyme that breaks up triglycerides -- stored fatty acids -- and converts them into usable fats for fuel in the hibernating ground squirrels. The second gene encodes the production of pyruvate dehydrogenase kinase isozyme 4 (PDK-4), an enzyme that is triggered during times of starvation and helps conserve the body's stores of glucose. Both genes are expressed in the squirrels' hearts at or just before the onset of hibernation.

Andrews' findings also may be of interest to evolutionary biologists. If hibernation is controlled by the differential expression of existing mammalian genes, as the research suggests, then the identification of these genes could provide insight into how other mammals could adapt (or how, long ago, their ancestors did adapt) to extreme environmental changes. In the future, they might even help scientists safely induce a hibernation-like state in astronauts during long-term space travel.

Andrews first reported the identification of the two genes in the Proceedings of the National Academy of Sciences in 1998. Since then, he and his team have mapped the genes, documented more fully how and when they're turned on in hibernating ground squirrels, and how this differs from their expression in nonhibernating mammals. (Pancreatic lipase (PL), for instance, is usually expressed in the pancreas of nonhibernating mammals, not the heart.) Further studies are being conducted on both summer-active and hibernating animals to identify and isolate additional gene sequences.

The study is funded by the North Carolina Biotechnology Center and the U.S. Army Research Office.

-- lucas --

NOTE TO EDITORS: A color photo of Dr. Matthew Andrews holding a hibernating ground squirrel is available at http://www2.ncsu.edu/ncsu/univ_relations/release.html (click on current releases and then on the story headline) or by calling NC State News Services at 919/515-3470. For a copy of Andrews' 1998 peer-reviewed article in the Proceedings of the National Academy of Sciences, contact Tim Lucas at the News Services number, or e-mail him at tim_lucas@ncsu.edu.